CN109862898A - The method and composition for the treatment of for wart - Google Patents

Abstract

Embodiment is related to including the composition for being greater than the stabilized hydrogen peroxide of 40%w/w to about 70%w/w.Composition can also include surface tension modifier (such as 2- propyl alcohol).Such composition can be used to treat the patient's condition (such as wart, condyloma acuminatum, molluscum contagiosum, or combinations thereof).Some embodiments also describe household compositions, office's composition, over the counter composition and the kit for using such composition.

Description

The method and composition for the treatment of for wart

Cross reference to related applications

This application claims the beauty of entitled " method and composition of the treatment for wart " submitted on August 17th, 2016 The priority of state's temporary patent application 62/376,326, content are integrally incorporated herein by reference.

Brief overview

Embodiment in the disclosure is related to including hydrogen peroxide composition.In some embodiments, composition may be used also To include alcohol.In some embodiments, hydrogen peroxide is stabilized hydrogen peroxide.In some embodiments, peroxidating Hydrogen can be standard level, food-grade, chemical synthesis grade, semiconductor grade, high test hydrogen peroxide grade, antibacterial grade, drinking water grade, doctor Medicine grade, active pharmaceutical ingredient (API) grade or cosmetics-stage hydrogen peroxide.In some embodiments, topical compositions include Greater than 40%w/w to the hydrogen peroxide of about 60%w/w.In some embodiments, topical compositions include about 45%w/w extremely The hydrogen peroxide of about 60%w/w.In some embodiments, the about 60%w/w of the amount of hydrogen peroxide up to composition.Some In embodiment, topical compositions include the hydrogen peroxide greater than 40%w/w to about 70%w/w.In some embodiments, Topical compositions include hydrogen peroxide of the about 45%w/w to about 70%w/w.In some embodiments, the amount of hydrogen peroxide The up to about 70%w/w of composition.In some embodiments, the amount of hydrogen peroxide is the about 60%w/w of composition.Some In embodiment, the amount of hydrogen peroxide is the about 59%w/w of composition.In some embodiments, the amount of hydrogen peroxide is group Close the about 55%w/w of object.In some embodiments, the amount of hydrogen peroxide is the about 54%w/w of composition.In some embodiment party In case, the amount of hydrogen peroxide is the about 50%w/w of composition.In some embodiments, topical compositions include about 45% The hydrogen peroxide of w/w.In some embodiments, alcohol can be selected from primary alconol, secondary alcohol, the tertiary alcohol or combinations thereof.In some embodiment party In case, alcohol can be selected from 2- propyl alcohol, methanol, butanol, 1- propyl alcohol, amylalcohol, hexanol, octanol, nonyl alcohol, decyl alcohol, 2- amylalcohol, 2- fourth Alcohol, benzylalcohol, ethyl alcohol, its isomers or combinations thereof.In some embodiments, the amount of alcohol is enough to reduce the surface of composition Power.In some embodiments, the about 5%w/w of the amount of alcohol up to composition.In some embodiments, composition is solution. In some embodiments, composition is gel preparation.In some embodiments, composition include can before the use, Two or more the individual components mixed when use or when close use.

Some embodiments are related to topical compositions, and the topical compositions include being greater than 0%w/w to about 60%w/ The hydrogen peroxide of w and 2- propyl alcohol greater than 0%w/w to about 10%w/w.Some embodiments are related to topical compositions, described Topical compositions include the hydrogen peroxide greater than 0%w/w to about 55%w/w and the 2- third greater than 0%w/w to about 10%w/w Alcohol.Some embodiments are related to topical compositions, and the topical compositions include the mistake greater than 0%w/w to about 54%w/w Hydrogen oxide and 2- propyl alcohol greater than 0%w/w to about 10%w/w.Some embodiments are related to topical compositions, and the part is used Composition includes the hydrogen peroxide greater than 0%w/w to about 50%w/w and the 2- propyl alcohol greater than 0%w/w to about 10%w/w.It is some Embodiment is related to topical compositions, and the topical compositions include the hydrogen peroxide greater than 0%w/w to about 45%w/w With the 2- propyl alcohol for being greater than 0%w/w to about 10%w/w.Some embodiments are related to topical compositions, the topical compositions 2- propyl alcohol including about 40%w/w to the hydrogen peroxide of about 60%w/w and greater than 0%w/w to about 10%w/w.Some embodiment party Case is related to topical compositions, the topical compositions amount of the including up to about hydrogen peroxide of 60%w/w and is greater than 0%w/w To the 2- propyl alcohol of about 5%w/w.Some embodiments are related to topical compositions, and the topical compositions include up to about The hydrogen peroxide of 60%w/w and 2- propyl alcohol greater than 0%w/w to about 2.5%w/w.In some embodiments, composition includes Hydrogen peroxide greater than 40%w/w and the 2- propyl alcohol greater than 0%w/w to about 10%w/w.In some embodiments, composition Including the hydrogen peroxide greater than 40%w/w to about 60%w/w and the 2- propyl alcohol greater than 0%w/w to about 10%w/w.In some realities It applies in scheme, composition includes the hydrogen peroxide of about 45%w/w and the 2- propyl alcohol greater than 0%w/w to about 10%w/w.Some In embodiment, composition includes the hydrogen peroxide greater than 40%w/w and the 2- propyl alcohol greater than 0%w/w to about 5%w/w.One In a little embodiments, composition includes the hydrogen peroxide greater than 40%w/w and the 2- propyl alcohol greater than 0%w/w to about 2.5%w/w. In some embodiments, composition includes the hydrogen peroxide of about 45%w/w and the 2- propyl alcohol greater than 0%w/w to about 5%w/w. In some embodiments, composition includes the hydrogen peroxide of about 45%w/w and the 2- propyl alcohol of about 5%w/w.In some embodiment party In case, composition includes the hydrogen peroxide of about 45%w/w and the 2- propyl alcohol of about 2.5%w/w.In some embodiments, 2- third The amount of alcohol is enough to reduce the surface tension of composition.In some embodiments, the amount of 2- propyl alcohol is enough to reduce the table of composition Face tension is enough to enhance infiltration of the composition into target skin area or target lesions.In some embodiments, surface The amount of power modifying agent is enough to enhance the therapeutic efficiency of composition.In some embodiments, hydrogen peroxide is stabilized peroxide Change hydrogen.In some embodiments, hydrogen peroxide is active pharmaceutical ingredient (API) grade hydrogen peroxide.In some embodiments, Topical compositions also include stabilizer.In some embodiments, stabilizer can be selected from stannate, sodium pyrophosphate, organic Phosphonate, nitrate, phosphoric acid, colloidal silicate, any stabilizer as known in the art or combinations thereof.In some embodiments In, the amount of 2- propyl alcohol is enough to reduce surface tension when being applied to target lesions, while minimizing composition to non-target skin The distribution of skin.In some embodiments, the amount of 2- propyl alcohol is enough to increase infiltration of the composition into target lesions.Composition can With 5 DEG C stablize at least about 2 years, 30 DEG C stablize at least about 12 months, 25 DEG C stablize at least about 12 months, in 5 DEG C of stabilizations At least about 12 months, 5 DEG C stablize at least about 6 months, 25 DEG C stablize at least about 6 months, 40 DEG C stablize at least about 6 Month, 5 DEG C stablize at least about 3 months, 25 DEG C stablize at least about 3 months, 40 DEG C of stable at least three moons, or combinations thereof.

In some embodiments, topical compositions have about 42mNm-1 to the surface of about 55mNm-1 at 37 DEG C Tension.In some embodiments, topical compositions include the stabilized cosmetics-stage hydrogen peroxide peace treaty of about 60%w/w The 2- propyl alcohol of 5%w/w, and wherein topical compositions are opened at 37 DEG C with about 42mNm-1 to the surface of about 55mNm-1 Power.In some embodiments, topical compositions include the stabilized cosmetics-stage hydrogen peroxide peace treaty of about 59%w/w The 2- propyl alcohol of 5%w/w, and wherein topical compositions are opened at 37 DEG C with about 42mNm-1 to the surface of about 55mNm-1 Power.In some embodiments, topical compositions include the stabilized cosmetics-stage hydrogen peroxide peace treaty of about 55%w/w The 2- propyl alcohol of 5%w/w, and wherein topical compositions are opened at 37 DEG C with about 42mNm-1 to the surface of about 55mNm-1 Power.In some embodiments, topical compositions include the stabilized cosmetics-stage hydrogen peroxide peace treaty of about 54%w/w The 2- propyl alcohol of 5%w/w, and wherein topical compositions are opened at 37 DEG C with about 42mNm-1 to the surface of about 55mNm-1 Power.In some embodiments, topical compositions include the stabilized cosmetics-stage hydrogen peroxide peace treaty of about 50%w/w The 2- propyl alcohol of 5%w/w, and wherein topical compositions are opened at 37 DEG C with about 42mNm-1 to the surface of about 55mNm-1 Power.In some embodiments, topical compositions include the stabilized cosmetics-stage hydrogen peroxide peace treaty of about 45%w/w The 2- propyl alcohol of 5%w/w, and wherein topical compositions are opened at 37 DEG C with about 42mNm-1 to the surface of about 55mNm-1 Power.In some embodiments, topical compositions include the stabilized cosmetics-stage hydrogen peroxide peace treaty of about 40%w/w The 2- propyl alcohol of 5%w/w, and wherein topical compositions are opened at 37 DEG C with about 42mNm-1 to the surface of about 55mNm-1 Power.In some embodiments, topical compositions include the stabilized cosmetics-stage hydrogen peroxide peace treaty of about 32.5%w/w The 2- propyl alcohol of 5%w/w, and wherein topical compositions are opened at 37 DEG C with about 42mNm-1 to the surface of about 55mNm-1 Power.In some embodiments, topical compositions include the stabilized cosmetics-stage hydrogen peroxide peace treaty of about 25%w/w The 2- propyl alcohol of 5%w/w, and wherein topical compositions are opened at 37 DEG C with about 42mNm-1 to the surface of about 55mNm-1 Power.

Some embodiments be related to include hydrogen peroxide and surface tension modifier composition.In some embodiments In, composition includes the up to about hydrogen peroxide of 60%w/w.In some embodiments, composition includes about 40%w/w or more More hydrogen peroxide.In some embodiments, composition includes hydrogen peroxide of the about 40%w/w to about 60%w/w.Some In embodiment, surface tension modifier is in the composition of hydrogen peroxide for including concentration disclosed in this paper embodiment Stable agent.In some embodiments, the amount of surface tension modifier is enough to enhance the therapeutic efficiency of composition.In some realities It applies in scheme, the amount of surface tension modifier is enough to change surface tension, while the stability of composition being maintained to be enough to act as quotient The feasible preparation of industry.In some embodiments, surface tension modifier is alcohol.In some embodiments, surface tension changes Property agent be 2- propyl alcohol.

Some embodiments describe the method for the treatment of wart, more the method includes having to subject in need application The topical compositions of hydrogen peroxide of about 60%w/w.In some embodiments, topical compositions further include alcohol.? In some embodiments, composition includes the up to about hydrogen peroxide of 50%w/w.In some embodiments, composition includes The up to about hydrogen peroxide of 45%w/w.In some embodiments, composition includes the hydrogen peroxide greater than 40%w/w.One In a little embodiments, composition includes hydrogen peroxide of the about 40%w/w to about 60%w/w.In some embodiments, composition Hydrogen peroxide including being greater than 40%w/w to about 60%w/w.In some embodiments, composition includes the mistake of about 59%w/w Hydrogen oxide.In some embodiments, composition includes the hydrogen peroxide of about 55%w/w.In some embodiments, composition Hydrogen peroxide including about 54%w/w.In some embodiments, composition includes the hydrogen peroxide of about 45%w/w.Some In embodiment, composition includes the hydrogen peroxide of about 45%w/w and the 2- propyl alcohol greater than 0%w/w to about 5%w/w.Some In embodiment, composition includes the hydrogen peroxide of about 45%w/w and the 2- propyl alcohol of about 5%w/w.In some embodiments, Composition includes the hydrogen peroxide of about 45%w/w and the 2- propyl alcohol of about 2.5%w/w.In some embodiments, composition includes The hydrogen peroxide of about 59%w/w and 2- propyl alcohol greater than 0%w/w to about 5%w/w.In some embodiments, composition includes The 2- propyl alcohol of the hydrogen peroxide of about 59%w/w and about 5%w/w.In some embodiments, composition includes about 59%w/w The 2- propyl alcohol of hydrogen peroxide and about 2.5%w/w.In some embodiments, composition include about 55%w/w hydrogen peroxide and Greater than the 2- propyl alcohol of 0%w/w to about 5%w/w.In some embodiments, composition include about 55%w/w hydrogen peroxide and The 2- propyl alcohol of about 5%w/w.In some embodiments, composition includes the hydrogen peroxide and about 2.5%w/w of about 55%w/w 2- propyl alcohol.In some embodiments, composition includes the hydrogen peroxide of about 54%w/w and greater than 0%w/w to about 5%w/w 2- propyl alcohol.In some embodiments, composition includes the hydrogen peroxide of about 54%w/w and the 2- propyl alcohol of about 5%w/w.One In a little embodiments, composition includes the hydrogen peroxide of about 54%w/w and the 2- propyl alcohol of about 2.5%w/w.

In some embodiments, wart can be the wart of virus induction.In some embodiments, wart can be selected from ordinary It is wart (verruca vulgaris (verruca vulgaris)), condyloma acuminatum, genital wart, external genital organs wart, palmoplantar verruca, mosaic warts, flat Wart, verruca filiformis, butcher's wart, oropharynx wart, anogenital wart, larynx wart, papilloma, dysplasia are (for example, CIN (epithelium of cervix uteri Interior tumor-like lesion)), duration wart, periungual wart, subungual wart, intractable wart, just control wart, see in epidermodysplasia verruciformis Cutaneous lesions, or combinations thereof.

The method of some embodiment description treatment molluscum contagiosums, the method includes applying to subject in need Composition with the up to about hydrogen peroxide of 60%w/w.In some embodiments, composition further includes alcohol.In some realities It applies in scheme, composition includes the hydrogen peroxide greater than 50%w/w.In some embodiments, composition includes being greater than 45% The hydrogen peroxide of w/w.In some embodiments, composition includes the hydrogen peroxide greater than 40%w/w.In some embodiments In, composition includes the hydrogen peroxide greater than 40%w/w to about 60%w/w.In some embodiments, composition includes about The hydrogen peroxide of 40%w/w to about 60%w/w.In some embodiments, composition include about 45%w/w hydrogen peroxide and Greater than the 2- propyl alcohol of 0%w/w to about 5%w/w.In some embodiments, composition include about 45%w/w hydrogen peroxide and The 2- propyl alcohol of about 5%w/w.In some embodiments, composition includes the hydrogen peroxide and about 2.5%w/w of about 45%w/w 2- propyl alcohol.In some embodiments, composition includes the hydrogen peroxide of about 59%w/w and greater than 0%w/w to about 5%w/w 2- propyl alcohol.In some embodiments, composition includes the hydrogen peroxide of about 59%w/w and the 2- propyl alcohol of about 5%w/w.One In a little embodiments, composition includes the hydrogen peroxide of about 59%w/w and the 2- propyl alcohol of about 2.5%w/w.In some embodiments In, composition includes the hydrogen peroxide of about 55%w/w and the 2- propyl alcohol greater than 0%w/w to about 5%w/w.In some embodiments In, composition includes the hydrogen peroxide of about 55%w/w and the 2- propyl alcohol of about 5%w/w.In some embodiments, composition packet Include the hydrogen peroxide of about 55%w/w and the 2- propyl alcohol of about 2.5%w/w.In some embodiments, composition includes about 54%w/ The hydrogen peroxide of w and 2- propyl alcohol greater than 0%w/w to about 5%w/w.In some embodiments, composition includes about 54%w/ The 2- propyl alcohol of the hydrogen peroxide of w and about 5%w/w.In some embodiments, composition includes the hydrogen peroxide of about 54%w/w The 2- propyl alcohol of about 2.5%w/w.

In some embodiments, the amount of alcohol can reduce the surface tension of composition.In some embodiments, 2- third The amount of alcohol is enough to reduce the surface tension of composition.In some embodiments, the amount of 2- propyl alcohol is enough to reduce the table of composition Face tension is enough to enhance infiltration of the composition into target skin area or target lesions.In some embodiments, surface The amount of power modifying agent is enough to enhance the therapeutic efficiency of composition.In some embodiments, the amount of alcohol can increase skin or skin The wettability of the surface of skin lesion.In some embodiments, the amount of alcohol can increase composition to the skin of subject and/or Permeability in cutaneous lesions.In some embodiments, the amount of 2- propyl alcohol is enough to increase infiltration of the composition into target lesions Thoroughly.In some embodiments, the amount of alcohol can enhance the clinical efficacy of composition.In some embodiments, the amount energy of alcohol Enough enhance the clinical efficacy of composition, while maintaining the enough stability for the composition of commericially feasible.

Some embodiments of this paper are related to topical solution preparation, and the topical solution preparation includes up to about 60% The hydrogen peroxide and alcohol of w/w.Some embodiments of this paper are related to topical solution preparation, and the topical solution preparation includes Greater than the hydrogen peroxide and alcohol of 40%w/w to about 60%w/w.In some embodiments, it when solution is included in application or is standing Two or more parts mixed before applying.

Some embodiments of this paper are related to gel combination, and the gel combination includes the up to about mistake of 60%w/w Hydrogen oxide, pure and mild gelling agent.Some embodiments of this paper are related to gel combination, and the gel combination includes being greater than 40% Hydrogen peroxide, the pure and mild gelling agent of w/w to about 60%w/w.In some embodiments, gel combination includes that can apply When or immediately apply before mix two or more parts.

Some embodiments of this paper are related to the kit for treating wart, and the kit includes container, the container Hydrogen peroxide including being greater than 40%w/w to about 60%w/w.In some embodiments, container further includes being greater than 0%w/w extremely The 2- propyl alcohol of about 5%w/w.In some embodiments, in the composition of 2- propyl alcohol and hydrogen peroxide in fragile container.One In a little embodiments, 2- propyl alcohol and hydrogen peroxide are separation in a reservoir.In some embodiments, 2- propyl alcohol and peroxidating Hydrogen can be in a separate container.In some embodiments, kit can also include gelling agent.In some embodiments, Container also includes applicator.In some embodiments, container is included in applicator.In some embodiments, container It is applicator.In some embodiments, kit also includes applicator.

Some embodiments of this paper describe a kind of group being substantially made of the up to about hydrogen peroxide of 60%w/w and alcohol Close object.Some embodiments of this paper describe a kind of composition being made of the up to about hydrogen peroxide of 60%w/w and alcohol.One In a little embodiments, alcohol is primary alconol, secondary alcohol, the tertiary alcohol or combinations thereof.In some embodiments, alcohol is not 1- propyl alcohol, ethyl alcohol, fourth Alcohol, amylalcohol, hexanol, octanol, nonyl alcohol, decyl alcohol, 2- butanol, 2- amylalcohol or benzylalcohol.In some embodiments, alcohol is 2- propyl alcohol.

Detailed description of the invention

Fig. 1 is illustrated after the hydrogen peroxide preparation for applying whole 40%w/w, and per unit area discharges in silicone film Average accumulated amount (the μ g/cm of hydrogen peroxide²).Each time point indicates average value ± SD (n=5-6).

Fig. 2 is illustrated after the hydrogen peroxide preparation for applying the 40%w/w containing 1- propyl alcohol, the per unit face in silicone film Average accumulated amount (the μ g/cm of the hydrogen peroxide of product release²).Each time point indicates average value ± SD (n=5-6).

Fig. 3 is illustrated after the hydrogen peroxide preparation for applying the 40%w/w containing 2- propyl alcohol, the per unit face in silicone film Average accumulated amount (the μ g/cm of the hydrogen peroxide of product release²).Each time point indicates average value ± SD (n=5-6).

Fig. 4 illustrates the hydrogen peroxide calculated between 0.5h and 4h after the hydrogen peroxide preparation for applying different propyl alcohol levels Steady state release amount (μ g/cm²/h).Each data point indicates average value ± SD, n=5-6.

The hydrogen peroxide that Fig. 5 illustrates 5%w/w, 10%w/w, 15%w/w and 20%w/w (1- propyl alcohol and 2- propyl alcohol) is steady Difference (flow [1- propyl alcohol]-flow [2- propyl alcohol]) in terms of state burst size.

Fig. 6 illustrates the average surface tension of the evaluated different hydrogen peroxide preparations containing 1- propyl alcohol or 2- propyl alcohol (mN/m)。

Fig. 7, which is illustrated, improves assessment score according to medical average wart.

Fig. 8 is illustrated according to medical wart seriousness assessment mean change of the score from baseline.

Fig. 9 illustrate in t=0h, 1h, 6h and for 24 hours, have skin and without skin in the case where contains 1- propyl alcohol and 2- propyl alcohol Whole 40%w/w hydrogen peroxide preparation redox potential (mV).Each time point indicates average value ± range, n =3.

Figure 10 illustrate in t=0h, 1h, 6h and for 24 hours, have skin and in the case where without skin, the 1- third containing 5%w/w The redox potential (mV) of the hydrogen peroxide preparation of the 40%w/w of the 2- propyl alcohol of alcohol or 5%w/w.Each time point indicates flat Mean value ± range, n=3.

Figure 11 depicts the illustrative applicator according to first embodiment.

Figure 12 illustrates doctor's wart when the 10th time medical and assesses mean change of (PWA) score from baseline.

Figure 13 illustrates the ratio for the subject for realizing that wart is removed when the 10th time medical.

Figure 14 illustrates the hydrogenperoxide steam generator treatment with 45%w/w for realizing that wart is removed when going to a doctor after each baseline The ratio of subject.

Figure 15 illustrates the hydrogen peroxide with 45%w/w that removing or slight PWA score are realized when the 10th time medical The ratio of the subject of Solution In The Treatment.

Figure 16 illustrates the peroxidating with 45%w/w that the reduction of 2 ordinal numbers of PWA score is realized when the 10th time medical The ratio of the subject of hydrogen solution treatment.

Figure 17 illustrates the hydrogenperoxide steam generator of 45%w/w, the hydrogenperoxide steam generator of 40%w/w and blank (vehicle) Each of when the 10th time medical local skin reaction, wherein 0=is reactionless；1=mild reaction；The reaction of 2=moderate.

Figure 18 illustrates the hydrogenperoxide steam generator for 45%w/w, part dermoreaction≤moderate when the 10th time medical Percentage.

Figure 19 illustrates the hydrogenperoxide steam generator for 40%w/w, part dermoreaction≤moderate when the 10th time medical Percentage.

Figure 20 is illustrated for blank (vehicle), part dermoreaction≤moderate percentage when the 10th time medical.

Figure 21 illustrates the 2- propyl alcohol in 12 months in the hydrogen peroxide of 5 DEG C of 45%w/w in 9mm ampoule and 5%w/w Solution (2.2ml) stability (as unit of the moon) (%w/w labelled amount) at any time.

Figure 22 illustrates in 12 months under the relative humidity (RH) of 25 DEG C and 60%w/w the 45%w/w in 9mm ampoule Hydrogen peroxide and 5%w/w 2- propanol solution (2.2ml) stability (as unit of the moon) (%w/w labelled amount) at any time.

Figure 23 illustrates in 6 months under the relative humidity (RH) of 40 DEG C and 75%w/w the 45%w/w in 9mm ampoule Hydrogen peroxide and 5%w/w 2- propanol solution (2.2ml) stability (as unit of the moon) (%w/w labelled amount) at any time.

It is described in detail

Before the present compositions and methods are described, it will be appreciated that the present invention is not limited to the certain parties of description Method, composition or methodology, because these can change.It will also be appreciated that terminology used herein is merely for description The purpose of specific version or embodiment, the range being not intended to limit the invention, the scope of the present invention is only by appended right It is required that limiting.Unless otherwise defined, whole technical terms and scientific terms used herein have such as the common skill in this field The identical meaning of the meaning that art personnel are generally understood.Although similar or equivalent to any method those of described herein and Material can be used in the practice or test of embodiment of the present invention, but will now be described be preferred method, device and Material.Whole publications mentioned by this paper are integrally incorporated by reference.Any content of this paper is not construed to recognize The present invention haves no right due to first invention prior to such disclosure.

It must further be noted that unless the context clearly indicates otherwise, otherwise such as institute in this paper and the appended claims It uses, singular " one (a) ", " one (an) " and " described " refer to comprising plural number.Thus, for example, to " cutaneous lesions " Refer to it being referring to one or more of cutaneous lesions well known by persons skilled in the art and its equivalent.

As it is used herein, term " about " means that the numerical value of its number currently in use adds deduct 2%w/w.Therefore, about 50%w/w is meant in the range of 49%-51%w/w.

When being used in combination with therapeutic agent, " application " mean therapeutic agent is applied directly to inside or on target tissue, Or therapeutic agent is applied to subject, the tissue that thus therapeutic agent targets it generates positive influence.Therefore, as used herein , when being used in combination with therapeutic agent, term administering " it may include (but being not limited to) for example, by being injected intravenously to subject Whole body provides therapeutic agent, and thus therapeutic agent reaches target tissue.Apply composition or therapeutic agent operation can for example, by injection, It is administered orally, local application, or is realized by the combination of these methods and other known technologies.Such combination technique can be with Use comprising heating, radiation, ultrasonic wave and delivery agents.Preferably, application is self application, and wherein therapeutic agent or composition are logical Subject oneself is crossed to apply.Alternatively, application can be the application from healthcare provider to subject.

When being used in combination with therapeutic agent, " offer " mean therapeutic agent is applied directly to inside or on target tissue, Or therapeutic agent is applied to subject, the tissue that thus therapeutic agent targets it generates positive influence.

As it is used herein, term " animal " is including (but not limited to) people and non-human vertebrate (such as wild animal, family Support animal and farm-animals).

As it is used herein, term " patient " or " subject " be the animal with deleterious conditions or the patient's condition (especially People), the disease or the patient's condition can be treated by therapeutic agent described herein and/or composition.

Term " improvement ", which be used to that embodiment change provided in this article be conveyed to provide it, apply or applying, to be controlled The feature and/or physical attribute of the tissue of the property treated composition.Term " improvement " can also be used in combination with morbid state, so that working as When morbid state " improvement ", symptom relevant to morbid state or physical features are weakened, reduce or eliminate.

Term " inhibition " is often referred to prevention paresthesia epilepsy, mitigates symptom or eliminates disease, the patient's condition or disorder.

It " optional " or " optionally " means that the event then described or situation can occur or can not occur, and retouches State include event there is a situation where and event not there is a situation where.

As it is used herein, room temperature " mean DEG C (room temperature of 68 ℉ to 77 ℉) from about 20 DEG C to about 25.

Through the description of the present application, using various terms, such as " main ", " secondary ", " first ", " second ". These terms are the convenient words for distinguishing different elements, and such term is not intended to be limited to and how can use not Same element.

When " pharmaceutically acceptable ", " physiologically tolerable " and its grammatical variants refer to composition, carrier, diluent It when with the other compositions of reagent or preparation, can be used interchangeably, and indicate that material can be administered without generating Reach the undesirable physiological effect (such as fash, calcination, stimulation or other ill-effects) of the intolerable degree of its recipient.

As it is used herein, when term " cosmetically acceptable " and its grammatical variants refer to composition, carrier, diluent When with the other compositions of reagent or preparation, indicate used in material and final composition it is overall to patient and especially pair No skin irritation is harmless in other respects, and preferably pleasant and with regard to overall appearance, pH, color, gas Well-tolerated for taste and quality (feeling), indicate it not and be for example unacceptable sticky (tacky), oiliness or it is dry It is dry, and indicate that it is easy to spread really, be absorbed into skin with acceptable absorption rate and usual moisturizing.

As it is used herein, term " therapeutic agent " is meant for treating, fighting, mitigate, prevent or improve subject's The medicament of unwanted conditions or disease.To a certain extent, embodiments described here can be related to various skin diseases, disease Condition or disorder or its symptom (including (but not limited to) the hyperplasia of prostate of skin, neoplasm, precancerous lesion or malignant tumour) are controlled Treat lesion.The patient's condition can be wart related conditions.The patient's condition can be the skin growth or hyperplasia of virus induction or non-viral induction. The patient's condition can selected from wart, verruca vulgaris (verruca vulgaris (verruca vulgaris)), condyloma acuminatum, genital wart, external genital organs wart, Palmoplantar verruca, mosaic warts, verruca plana, verruca filiformis, butcher's wart, oropharynx wart, anogenital wart, larynx wart, papilloma, dysplasia (for example, CIN (cervical intraepithelial neoplasia (CIN))), duration wart, subungual wart, intractable wart, just control wart, see wart periungual wart Cutaneous lesions, molluscum contagiosum in shape epidermodysplasia, or combinations thereof.

As it is used herein, term " stabilized hydrogen peroxide " refers to the peroxide including stabilizer or stabilizer admixture Change hydrogen, the stabilizer for hydrogen peroxide is diluted to can mix in stable commercial formulations to cutaneous lesions locally apply with The concentration for treating skin conditions described herein.In some embodiments, hydrogen peroxide can be obtained from commercial source.It crosses It is proprietary and/or commercially secret that the amount and type of one or more stabilizers used in hydrogen oxide preparation can be commercial source It is close.In some embodiments, stabilized hydrogen peroxide is the hydrogen peroxide of high concentration.Although the pure hydrogen peroxide of high concentration It is usually stable, but when the usual acquisition by commercial source, stabilizer can be used, in hydrogen peroxide preparation so as to steady The dilute form of fixed " high concentration " hydrogen peroxide preparation.Some hydrogen peroxide preparations have concentration (total and/or individual) foot To provide the stabilized stabilizer of the diluted hydrogen peroxide for special-purpose or specific industry.In some embodiments In, stabilized hydrogen peroxide is ratified via Food and Drug Administration (FDA) for people's local application.In some implementations In scheme, stabilized hydrogen peroxide has drug master file (drug master file) in FDA, and ratifies to use by FDA In to people's local application.

As it is used herein, term " clinical efficacy " refers to that ingredient or composition generate the ability of desired effect.For example, In some embodiments, it is desirable that effect may include and (be not limited to) surface tension for reducing composition, increase skin or skin The surface wettability of skin lesion increases composition and enters the skin, cutaneous lesions or surface defect of subject (comprising skin or skin Crack, invagination and the irregularity of skin lesion) in permeability, reduce the size of target lesion, improve target lesion shape and/or Appearance improves target lesion or treatment region, and/or removal target lesion, or combinations thereof.

As it is used herein, term " treatment is effective " or " effective ", can be used interchangeably, and refer to this The amount of the therapeutic combination of embodiment described in text.For example, the treatment of composition effectively measure be composition (and especially Be active constituent, such as hydrogen peroxide) generally reach the amount of desired effect.

" the effective amount for the treatment of " of composition or " effective amount " are amounts necessary to reaching desired result or are enough to obtain Obtain the amount of desired result.Activity expected from this paper embodiment includes that (depending on the circumstances) medical thera-peutic is treated, beauty is controlled The property treated treatment and/or the treatment of prevention disease.Embodiment application according to the present invention is to obtain therapeutic effect and/or prevention Property effect the specific dosage of compound will be determined certainly by the specific condition around case, including, for example, the change applied Close object, administration method and the patient's condition being treated.However, the effective amount of application can be by practitioner or manufacturer or patient According to correlation circumstance (selection and selected administration method comprising the patient's condition to be treated, compound to be administered) come really It is fixed, and therefore, the above dosage range is not intended to limit the scope of the invention in any way.The chemical combination of this paper embodiment The treatment of object, which is effectively measured, to be usually such that and is administered when in the compound in a physiologically tolerable vehicle composition When, it is sufficient in the tissue or tissue reaches effective system concentration or local concentration to obtain desired treatment results or clinic As a result amount.

As it is used herein, term " treatment (treat) ", " treatment (treated) " or " treatment (treating) " refers to Therapeutic treatment, cosmetic treatment, and/or prevention against disease or preventive measure, wherein purpose is to prevent or slow down (to subtract Gently) the undesirable physiology patient's condition, disorder or disease, or obtain beneficial or desired clinical effectiveness.For the disclosure Purpose, mitigation of the beneficial or desired clinical effectiveness including (but not limited to) symptom；The degree of the patient's condition, disorder or disease subtracts It is weak；The stabilization (that is, not deteriorating) of the state of the patient's condition, disorder or disease；The patient's condition, the delay of disorder or the breaking-out of disease or the patient's condition, The progress of disorder or disease slows down；The patient's condition, disorder or the mitigation of morbid state；With the alleviation of the patient's condition, disorder or disease (no matter It is all or part of), the either detectable or undetectable or patient's condition, disorder or the improvement of disease (enhancement) or improve.Treatment is comprising causing clinically significantly to respond, and the side effect without excessive level.

As it is used herein, term " by ... form (consist of) " or " by ... it forms It is specific in the embodiment or claim of particular requirement protection that (consisting of) " means that preparation or method are only contained in Element, step or the ingredient enumerated.

As it is used herein, term " substantially by ... form (consisting essentially of) " or " substantially by ... form (consist essentially of) " mean preparation or method only and include specified material or Step and those of essential characteristic and the novel feature for not influencing claimed invention substantially.

Typically, term " tissue " refers to any aggregation of similar specialized cell, joins together to complete specific function Energy.

Wart (wart) is the lesion of virus induction, is caused by the hypotype of skin human papilloma virus (HPV) family.HPV type is The mankind can be infected and cause the subclass of the major class of the DNA papillomavirus family of cutaneous lesions.HPV is prevalent in environment In and due to clinically (obvious lesion) or the virulent individual of subclinical direct contact tool, indirectly by being exposed to Contaminated surface occurs most frequently infection from individual lesion to the adjacent autoinoculation for being uninfected by skin by virus.HPV infection Cutaneous manifestations include verruca vulgaris (verruca vulgaris (verruca vulgaris)), palmoplantar verruca, mosaic warts, verruca plana, butcher's wart etc.. The hypotype of HPV family is also oropharynx wart, anogenital wart, larynx wart, papilloma, dysplasia (for example, CIN (epithelium of cervix uteri Interior tumor-like lesion), carcinoma in situ, cancer and the cause of disease for seeing the cutaneous lesions in epidermodysplasia verruciformis.Verruca vulgaris is usually angle Change excessive, external cheese papule or tubercle (usually related to 1 type, 2 types or 4 type HPV) and be most frequently located in finger and (includes First week region and first under region), the back side of hand, be easy to happen the position (for example, knee, elbow) of wound, but may almost appoint What his anatomical location occurs.

Condyloma acuminatum (being more commonly referred to as genital wart) usually with 6 types and 11 types, 16 types, 18 type HPV and many other Asias Type (for example, 33,35,39,40,43,45,51-56,58 etc.) is related, and may exist a variety of hypotypes in single lesion. Condyloma acuminatum typically appear as it is single to multiple meats, molluscum sample papule, the papule can for cheese, filiform, gill fungus shape, " cauliflower-like " or form fusion patch.They are usually located at anogenital region (for example, penis, vulva, vagina, cervix, meeting Yin and perianal region), and it possibly is present at oropharynx, larynx and even in tunica mucosa tracheae, and appear in other skin positions rarely Set (for example, trunk, four limbs).Lesion be usually it is benign, but certain HPV hypotypes it is related to the risk of malignant potential (for example, HPV hypotype 16,18), and may cause cutaneum carcinoma or carcinoma in situ (such as bowenoid papulosis (bowenoid papulosis) or Bu-column tumor (Buschke-Lowenstein tumor)) and cervical atypical hyperplasia or tumor-like lesion (for example, in epithelium of cervix uteri Tumor-like lesion (CIN)).

In the normal individual of immune function, many common skin lesions (for example, wart and condyloma) relevant to HPV infection The spontaneous regression within the time less than 2 years.However, wart can be it is big and/or cosmetically unhandsome (for example, face, hand), Distal side anatomic region is spread to by autoinoculation, is to make us pain (for example, by wound or in sole), and just control wart Significant HPV infection reservoir is provided in group.

There is currently no the specific antiviral therapies that can be used for treating skin HPV infection.Therefore existing therapy is for use Focal destructive mode is to the direct physical damage of lesion, such as cold therapy, electrosurgery, curettage, the application of laser therapy, acid (for example, salicylic acid, trichloroacetic acid)；Localized cytotoxicity therapy, if part is in podophyllin, cantharidin or part or lesion 5 FU 5 fluorouracil or bleomycin；Immunosuppressant therapy therapy is (for example, candida antigens, office in part imiquimod, lesion Use side, portion dibutyl phthalate, oral Cimetidine) or the removal of surgery lesion.These various therapies can also be used as non-under low concentration Prescription (OTC) wart therapy is (for example, part salicylic acid dosage form；Household " freezing " kit).Although these methods can be one Cure rate is realized in a little cases, but much equipment for needing to doctor's office repeatedly medical, Specialized training and use valuableness； They be make us pain and may need to anaesthetize and/or relieve pain, and they can concurrent unfavorable esthetic result, comprising controlling Treat the cicatrization at site and the risk of typical postoperative hemorrhage and infection.There is no a kind of therapy to be in all cases Continuous and effective, and in fact, exist in the used method using each in these technologies between practitioner As a result very big changeability also has very big changeability.Recurrence is common, and a variety of therapeutic modalities are applied in combination and often realize Necessary to significantly improving.Therefore, to for cutaneous lesions relevant to HPV infection (for example, wart and condyloma) in this field Safely and effectively there are the needs not being able to satisfy greatly very much in local treatment.

Molluscum is the lesion of virus induction, is caused by the hypotype of the DNA poxvirus family of mollascus contagiosum virus (MCV). There are the MCV of four kinds of hypotypes, (MCV-1 to MCV-4), wherein MCV-1 is most universal, and MCV-2 is most common in adult.And HPV Equally, MCV is prevalent in environment, and due to virulent in clinical (obvious lesion) or subclinical upper directly contact tool Individual, indirectly by being exposed to contaminated surface or be uninfected by itself connecing for skin from individual lesion to adjacent by virus It plants and occurs most frequently infection.Infection is most commonly in the active adult and immunocompromised person of children population, sexual life.Infectiousness Molluscum lesion is usually yellowish pink, cheese umbilical (" recess ") papule, the papule can individually or in cluster appearance and Although any region of skin can be appeared in, it is usually located at trunk groin or four limbs.Individual lesions can be in several weeks Spontaneous regression in the several months, however, continuing occurs to the infection natural history that lesion at last one subsides in lesion from first Six months to 5 years or longer time.

Currently without the treatment to molluscum contagiosum ratified through United States Food and Drag Administration.Currently without can be used for The specific antiviral therapy for treating skin MCV infection.Therefore existing therapy is directed to focal destructive mode to the straight of lesion Physical damage is connect, such as cold therapy, electrosurgery, curettage, laser therapy, be that lesion goes to top (" needle is chosen "), application with such as needle Acid or caustic (for example, salicylic acid, potassium hydroxide)；Localized cytotoxicity therapy, such as part podophyllin, cantharidin； Immunosuppressant therapy therapy (for example, candida antigens, nitric acid, oral Cimetidine in part imiquimod, lesion) or outer The removal of section's lesion.Although these methods can realize cure rate in some cases, it is many need it is multiple to doctor's office Medical, Specialized training and the equipment for using valuableness；They may be making us pain and may need to anaesthetize and/or only Bitterly, and there may be anxieties and psychic trauma, especially in child age group.These treatments can concurrent unfavorable beauty knot Fruit includes cicatrization, bleeding and the sense at pigment change (both hyperpigmentation and hypopigmentation), treatment site Dye.Not having a kind of therapy is continuous and effective in all cases, and in fact, uses this used between practitioner There is very big changeability in the method for each in a little technologies, as a result also there is very big changeability.A variety for the treatment of sides are applied in combination Formula (comprising treating the potential local patient's condition (such as atopic dermatitis) tending to be susceptible to suffer from molluscum and lesion and spreading) is often realized aobvious It writes necessary to improving.Therefore, it safely and effectively (part) is treated in this field to for cutaneous lesions relevant to MCV infection In the presence of the needs not being able to satisfy greatly very much.

Hydrogen peroxide (H₂O₂) it is compound generally existing in the environment.It is simplest peroxide and is nothing Common potent oxidant in number household supplies (include bleaching agent for unchlorine, universal cleaning products and disinfectant), by with Make the oxidation component in hair dyes, and has been used in dental health product and dental whitening systems for many years.In industry On, it is used for the processing of waste water and at high concentrations, is used for bleached paper, paper pulp and textile.Clinically, in addition to It is used as outside oral local application's agent as described above, and hydrogen peroxide is widely used as wound at low concentrations (for example, 3%-6%) Irrigation and part antibacterial/disinfectant agents, and since 1858 are introduced into clinical practice by Richardson It medically uses always.

Hydrogen peroxide is the important oxidant in biosystem.Local detrimental effect resisting because of complexity of the active oxygen to skin The presence of oxidant defense system and mitigate, the system include enzyme (such as catalase, glutathione peroxidase, superoxides discrimination Change enzyme, thioredoxin reductase, lipoamide, lipid peroxidase etc.) and non-enzymatic component (comprising ascorbic acid, Lithate and uric acid, tocopherol, glutathione, ubiquinone, panthenol and other water soluble groups).Part applies supraphysiologic levels Hydrogen peroxide can defeat the Antioxidative Defense System in skin, and hydrogen peroxide is allowed to have unit not only through its direct oxidation It knits, generate active oxygen and local lipid peroxidation and work, but also by generating to abnormality (for example, wart, sharp wet Wart, molluscum contagiosum) the toxic local concentration of cell oxygen and work.

Also unexpectedly observe, after the composition for applying this paper embodiment, verruca vulgaris (verruca vulgaris (verruca vulgaris)) lesion display clinical response.In certain cases, cutaneous lesions are observed after single therapy Improvement, reduction or removing.In other cases, for example, with duration, recurrent, intractable lesion or suffering from thicker disease In the case of change or larger lesion, clinical response may need to treat two or more times.In certain cases, controlled a series of The improvement or removing of cutaneous lesions are observed after treating and (treating once a week).As the example benefit of this treatment method, Clinical response is well-tolerated and is caused without analgesic, will not induce pain and will not induce usually by other treatments Significant adverse events and unfavorable esthetic result caused by method, e.g., for example, (such as hypopigmentation or pigment are heavy for pigment change It is excessive), cicatrization, bleeding or infection at treatment site.

Embodiments herein relate generally to include hydrogen peroxide composition.In some embodiments, composition It can also include surface tension modifier.In some embodiments, surface tension modifier is including this paper embodiment Disclosed in each concentration hydrogen peroxide composition in stable agent.In some embodiments, surface tension modifier Amount is enough to enhance the therapeutic efficiency of composition.In some embodiments, the amount of 2- propyl alcohol is enough to increase composition to target disease Infiltration in change.In some embodiments, the amount of 2- propyl alcohol is enough to increase infiltration of the composition into target lesions.Some In embodiment, the amount of surface tension modifier is enough to enhance the therapeutic efficiency of composition, while maintaining the stability of composition. In some embodiments, the amount of surface tension modifier is enough to enhance the therapeutic efficiency of composition, while maintaining composition Stability is enough to act as the preparation of commericially feasible.In some embodiments, surface tension modifier is alcohol.The embodiment party of this paper Case further relate to include hydrogen peroxide and alcohol composition.In some embodiments, hydrogen peroxide can be standard level, food Grade, chemical synthesis grade, semiconductor grade, high test hydrogen peroxide grade, antibacterial grade, drinking water grade, pharmaceutical grade or cosmetics-stage peroxide Change hydrogen.In some embodiments, alcohol can be selected from primary alconol, secondary alcohol, the tertiary alcohol or combinations thereof.In some embodiments, alcohol can To be selected from (but being not limited to) low-molecular-weight alcohol, such as methanol, ethyl alcohol, butanol, 1- propyl alcohol, amylalcohol, hexanol, octanol, nonyl alcohol, decyl alcohol, 2- butanol, 2- propyl alcohol, 2- amylalcohol, benzylalcohol, its isomers or combinations thereof.In some embodiments, alcohol is not 1- propyl alcohol, second Alcohol, propyl alcohol, butanol, amylalcohol, hexanol, octanol, nonyl alcohol, decyl alcohol, 2- butanol, 2- amylalcohol or benzylalcohol.In some embodiments, alcohol For 2- propyl alcohol (also referred to as isopropanol).In some embodiments, other volatile matters are (e.g., for example, acetic acid esters (such as ethyl acetate With butyl acetate (volatile matter used in nail polish)), cyclomethicone (may be embodied in the volatility silicon in emulsifier system Ketone) it can be applied in combination with alcohol or alcohol is replaced to use.Embodiments herein also includes substantially to be made of hydrogen peroxide and alcohol Composition.Some embodiments are related to the composition being made of hydrogen peroxide and alcohol.Some embodiments are related to including peroxide Change the composition of hydrogen and 2- propyl alcohol.Some embodiments are related to the composition being substantially made of hydrogen peroxide and 2- propyl alcohol.One A little embodiments are related to the composition being made of hydrogen peroxide and 2- propyl alcohol.

In some embodiments, the amount of hydrogen peroxide is up to the about 60%w/w of composition.In some embodiments, The amount of hydrogen peroxide is up to the about 55%w/w of composition.In some embodiments, the amount of hydrogen peroxide is up to the pact of composition 50%w/w.In some embodiments, the amount of hydrogen peroxide is up to the about 45%w/w of composition.In some embodiments, The amount of hydrogen peroxide is greater than 40%w/w.In some embodiments, the amount of hydrogen peroxide is greater than 40%w/w to about 60%w/ w.In some embodiments, the amount of hydrogen peroxide is about 45%w/w.In some embodiments, the amount of hydrogen peroxide is about 55%w/w.In some embodiments, the amount of hydrogen peroxide is about 54%w/w.In some embodiments, hydrogen peroxide Amount is about 59%w/w.In some embodiments, composition includes hydrogen peroxide, and the amount of the hydrogen peroxide is about 0.5%w/ W to about 99.9%w/w, about 10%w/w are to about 99.9%w/w, about 20%w/w to about 99.9%w/w, about 30%w/w to about 99.9%w/w, about 40%w/w are to about 99.9%w/w, about 50%w/w to about 99.9%w/w, about 60%w/w to about 99.9%w/ W, about 70%w/w to about 99.9%w/w, about 80%w/w to about 99.9%w/w, about 90%w/w to about 99.9%w/w, about 0.5%w/w to about 70%w/w, about 5%w/w are to about 70%w/w, about 10%w/w to about 70%w/w, about 15%w/w to about 70%w/w, about 20%w/w are to about 70%w/w, about 25%w/w to about 70%w/w, about 30%w/w to about 70%w/w, about 35% W/w to about 70%w/w, about 40%w/w are to about 70%w/w, about 40.5%w/w to about 70%w/w, about 41%w/w to about 70% W/w, about 41.5%w/w are to about 70%w/w, about 42%w/w to about 70%w/w, about 42.5%w/w to about 70%w/w, about 43% W/w to about 70%w/w, about 43.5%w/w are to about 70%w/w, about 44%w/w to about 70%w/w, about 44.5%w/w to about 70%w/w, about 45%w/w are to about 70%w/w, about 50%w/w to about 70%w/w, about 55%w/w to about 70%w/w, about 60% W/w to about 70%w/w, about 65%w/w to about 70%w/w, be up to about 60%w/w, about 0.5%w/w to about 60%w/w, about 5% W/w to about 60%w/w, about 10%w/w are to about 60%w/w, about 15%w/w to about 60%w/w, about 20%w/w to about 60%w/ W, about 23.5%w/w to about 60%w/w, about 25%w/w are to about 60%w/w, about 30%w/w to about 60%w/w, about 35%w/w To about 60%w/w, about 40%w/w to about 60%w/w, about 40.5%w/w to about 60%w/w, about 41%w/w to about 60%w/w, About 41.5%w/w to about 60%w/w, about 42%w/w are to about 60%w/w, about 42.5%w/w to about 60%w/w, about 43%w/w To about 60%w/w, about 43.5%w/w to about 60%w/w, about 44%w/w to about 60%w/w, about 44.5%w/w to about 60%w/ W, about 45%w/w to about 60%w/w, be up to about 50%w/w, about 0.5%w/w to about 50%w/w, about 5%w/w to about 50%w/ W, about 10%w/w to about 50%w/w, about 15%w/w are to about 50%w/w, about 20%w/w to about 50%w/w, about 23.5%w/w To about 50%w/w, about 25%w/w to about 50%w/w, about 30%w/w to about 50%w/w, about 35%w/w to about 50%w/w, about 40%w/w to about 50%w/w, about 40.5%w/w to about 50%w/w, about 41%w/w to about 50%w/w, about 41.5%w/w extremely About 50%w/w, about 42%w/w to about 50%w/w, about 42.5%w/w to about 50%w/w, about 43%w/w to about 50%w/w, about 43.5%w/w to about 50%w/w, about 44%w/w are to about 50%w/w, about 44.5%w/w to about 50%w/w or about 45%w/w To about 50%w/w.In some embodiments, the amount of hydrogen peroxide can be about 0.5%w/w, about 5%w/w, about 10%w/w, About 15%w/w, about 20%w/w, about 23.5%w/w, about 25%w/w, about 30%w/w, about 32.5%w/w, about 35%w/w, about 40%w/w, about 40.5%w/w, about 41%w/w, about 41.5%w/w, about 42%w/w, about 42.5%w/w, about 43%w/w, about 43.5%w/w, about 44%w/w, about 44.5%w/w, about 45%w/w, about 46%w/w, about 47%w/w, about 48%w/w, about 49%w/w, about 50%w/w, about 51%w/w, about 52%w/w, about 53%w/w, about 54%w/w, about 55%w/w, about 56%w/ W, any two in about 57%w/w, about 58%w/w, about 59%w/w, about 60%w/w, about 65%w/w, about 70%w/w or these values A range.

In some embodiments, hydrogen peroxide can be stabilized hydrogen peroxide.In some embodiments, peroxide Change hydrogen can be standard level, food-grade, chemical synthesis grade, semiconductor grade, high test hydrogen peroxide grade, antibacterial grade, drinking water grade, Pharmaceutical grade, active medicine grade ingredient (API) grade or cosmetics-stage hydrogen peroxide.In some embodiments, hydrogen peroxide can be with It is stabilized pharmaceutical grade hydrogen peroxide.In some embodiments, hydrogen peroxide can be active pharmaceutical ingredient (API) grade mistake Hydrogen oxide.In some embodiments, hydrogen peroxide is FMC/PeroxyChem 50%w/w " api class " hydrogen peroxide.One In a little embodiments, hydrogen peroxide is FMC/PeroxyChem 59%w/w " api class " hydrogen peroxide.In some embodiments In, hydrogen peroxide is FMC/PeroxyChem 70%w/w " api class " hydrogen peroxide.In some embodiments, hydrogen peroxide It can be stabilized cosmetics-stage hydrogen peroxide.In some embodiments, hydrogen peroxide is FMC/PeroxyChem " Super D " 50%w/w cosmetics-stage hydrogen peroxide.In some embodiments, hydrogen peroxide is FMC/PeroxyChem " height test hydrogen peroxide ", it includes the stabilized hydrogen peroxide of 50%w/w, 70%w/w and 90%w/w.In some implementations In scheme, hydrogen peroxide is 50 CG of Arkema Peroxal.In some embodiments, initial hydrogen peroxide concentration is at this Be enough to be diluted in composition described in text the hydrogen peroxide of about 23%w/w or more than concentration concentration.In some realities It applies in scheme, stabilized hydrogen peroxide has in the mistake that it is diluted to about 23%w/w in compositions described herein Hydrogen oxide or more than concentration when, it is sufficient to prevent the stabilizer of hydrogen peroxide decomposition/degradation concentration.In some embodiments In, stabilized hydrogen peroxide has in the hydrogen peroxide that it is diluted to about 23%w/w in compositions described herein Or when above concentration, it is sufficient to prevent the stabilization of surface tension modifier (for example, alcohol, such as 2- propyl alcohol) decomposition/degradation concentration Agent.In some embodiments, stabilized hydrogen peroxide, which has, is enough to ensure that and to be packaged in appropriate packaging system, container or applies Add the stability of the composition in device, and it is desired in embodiment as described herein as, be suitable for business and use Concentration stabilizer.For example, in some embodiments, the method for manufacturing composition may include in the final composition will The dilution of stabilized hydrogen peroxide to such as 59%w/w, 55%w/w, 54%w/w, 50%w/w, 45%w/w or 40%w/w or A step of 32.5%w/w or 25%w/w or multiple steps.In this case, initial hydrogen peroxide preparation should have Sufficiently high concentration is so as to addition water (such as deionized water) and a kind of additional excipient or a variety of excipient (such as tables Face tension modifier (such as alcohol (for example, 2- propyl alcohol)) be diluted to such as 59%w/w, 55%w/w, 54%w/w, 50%w/w, 45%w/w or 40%w/w or 32.5%w/w or 25%w/w, as described in this paper embodiment, so that it is abundant It stabilizes, to guarantee the shelf life for being suitable for producing the feasible preparation of business.

Hydrogen peroxide is a kind of compound very easily decomposed due to there are dissolved impurity, mainly transition metal sun Ion and mixture potentially unstable based on hydrogen peroxide, wherein concentration of hydrogen peroxide subtracts at any time due to catalytic decomposition It is small.The impurity for causing hydrogen peroxide to decompose is generally contained in for aqueous hydrogen peroxide bulk formulation to be diluted to desired concentration In water or it is contained in the additional excipients (for example, 2- propyl alcohol) being added in preparation.Various factors can influence mistake in solution The stability of hydrogen oxide, the factor is including, for example, temperature, the concentration of hydrogen peroxide, pH value and the impurity with decomposition Presence.In order to limit such influence of the separation factors to stability, it has been found that, in some embodiments, for this The commercially valuable stabilisation of the treatment of multiple dermatosis condition described in text (for example, wart, condyloma acuminatum, molluscum contagiosum) Composition can be by selecting 2- propyl alcohol and stabilized (for example, cosmetics-stage) high concentration (for example, 50%) peroxide with caution Change the concentration of aqueous solution of hydrogen to realize.Therefore, in some embodiments, composition may include the group of stabilizer or stabilizer It closes.Hydrogen peroxide product from separate sources can be unique proprietary because of each production line in each company and each company Stabilizer admixture and it is different, and can stability to final products and performance have an important influence on.Every kind individually steady Determine agent stabilizer level from 0mg/ml to change between thousands of mg/l, can each depend on the grade of hydrogen peroxide, The selection of the concentration of peroxide and used stabilizer.In some embodiments, hydrogen peroxide is by FMC Industrial (present PeroxyChem, LLC.), SigmaArkemaDeng supply.In some embodiments, hydrogen peroxide is supplied by PeroxyChem, LLC.In some embodiment party In case, hydrogen peroxide is FMC/PeroxyChem " Super D " 50%w/w cosmetics-stage hydrogen peroxide.In hydrogen peroxide preparation The common stabilizer for being included may include stannate (for example, colloid stannate, sodium stannate), sodium pyrophosphate, organic phosphonate, Nitrate, phosphoric acid, colloidal silicate, any other stabilizer as known in the art, or combinations thereof.In some embodiments In, the concentration of every kind of stabilizer can be 0ppm up to about 5000ppm.In some embodiments, every kind of stabilizer is dense Degree can be 0ppm up to about 3000ppm.In some embodiments, the concentration of every kind of stabilizer can be about 70ppm extremely About 5000ppm.In some embodiments, the concentration of every kind of stabilizer can be about 70ppm to about 3000ppm.In some realities It applies in scheme, the concentration of every kind of stabilizer can be about 70ppm to about 2700ppm.In some embodiments, every kind of stabilizer Concentration can be about 270ppm to about 5000ppm.In some embodiments, the concentration of every kind of stabilizer can be about 300ppm to about 5000ppm.In some embodiments, the concentration of every kind of stabilizer can be about 270ppm to about 3000ppm. In some embodiments, the concentration of every kind of stabilizer can be about 300ppm to about 3000ppm.In some embodiments, The concentration of every kind of stabilizer can be about 300ppm to about 2700ppm.In some embodiments, the concentration of every kind of stabilizer can Think about 270ppm to about 2700ppm.

Hydrogen peroxide in the composition of this paper embodiment can be replaced with other peroxide or with other peroxidating Object combination.Other peroxide may include (but being not limited to) sodium peroxide, potassium peroxide and potassium superoxide, lithium peroxide, mistake Barium monoxide, calper calcium peroxide, peromag, zinc peroxide, tert-butyl hydroperoxide, peracetic acid, peroxidating dibenzyl, benzoyl peroxide Formyl, lauroyl peroxide or combinations thereof.

Water, organic solvent (such as alcohol), surfactant and other agent can change composition, preparation, and most especially It is the surface tension of solution.However, the alcohol of low concentration or other volatile matters are to normal skin when about applying alcohol/aqueous mixtures The influence of wetability know little about it, and be impregnated in about the alcohol of various concentration or other volatile matters including hydrogen peroxide To the wetability of normal skin or to abnormal skin or affected skin (as being subjected to wart, condyloma acuminatum, infectiousness when in preparation The skin growth or cutaneous lesions of molluscum or other virus inductions or the skin growth or cutaneous lesions of non-viral induction influence Skin) the influence of wetability there is no report.It is not bound to theory, it is believed that can comprising alcohol in stabilized peroxide solutions To play several important functions: the alcohol (for example, the 2- propyl alcohol for being less than 15%w/w) for mixing low concentration can permit incorporation treatment The hydrogen peroxide (for example, hydrogen peroxide of 25%w/w to 60%w/w) of effective concentration, wherein hydrogen peroxide can be enough Concentration is to realize the desired therapeutic effect to cutaneous lesions, and the amount of alcohol is enough to reduce the surface tension of preparation and be enough Increase cutaneous lesions wettability of the surface, to allow preparation to spread on the surface and enter at the surface imperfection of lesion.? In some embodiments, the amount of alcohol is enough to increase infiltration of the composition into target lesions.However, secondary alcohol is (for example, isopropanol (IPA)) inherent stability being expected in the hydrogen peroxide of high concentration is poorer than primary alconol (seeing below), that is, 2- propyl alcohol is expected It is more oxidizable than 1- propyl alcohol in the hydrogen peroxide of high concentration, and incorporation of concentration is sufficient for requirements above and (reduces surface Wetability/the maintenance of power/increase cutaneous lesions enhances therapeutic efficiency and increases infiltration of the composition into target lesions) Low concentration secondary alcohol (IPA) and the preparation for allowing to generate stable commericially feasible is challenging.

It has surprisingly been found that can steadily incorporation can be enough to reduce into highly concentrated hydrogenperoxide steam generator The surface tension of preparation can increase cutaneous lesions wettability of the surface and can maintain or enhance preparation to for the application The 2- propyl alcohol of the therapeutic effect of the patient's condition of theme.As described above, isopropanol (a kind of secondary alcohol) is expected at the mistake there are high concentration It is more oxidizable than 1- propyl alcohol (a kind of primary alconol) in the case where hydrogen oxide.It is not wishing to be bound by theory, in the hydrogen peroxide of high concentration The oxidation mechanism of middle alcohol is to generate hydroxyl radical free radical by the decomposition of hydrogen peroxide first.This process can by catalytic metal or Other catalyst (may such as pass through the catalysis of those of addition excipient and/or impurity (mainly transition-metal cation) introducing Agent) presence and accelerate.Then a hydrogen atom is extracted on the carbon that hydroxyl radical free radical can be adjacent with oxygen from alcohol molecule, generates carbon Free radical.In the case where isopropanol, this is secondary free radical, and the secondary free radical is by electronics on oxygen and close to two of carbon Methyl group and it is stabilized.For 1- propyl alcohol, this is the primary free radical only with a close alkyl group therewith, Its less stable and it is more difficult to be formed.The hydrogen atom for losing hydroxyl group is formed ketone or aldehyde, and aldehyde by this intermediate product (propionic aldehyde from 1- propyl alcohol) can be further oxided as propionic acid.High-purity and by highly stableization or have high concentration In the preparation of the hydrogen peroxide of stabilizer (and catalyst/impurity with low concentration), the decomposition of peroxide can be slowed down, And it can therefore slow down the decomposition of included alcohol.Although the decomposition of peroxide is slow without obvious catalyst Slowly.Apparent reaction rates may be to be related to the complexity of any traces of catalyst (for example, catalytic metal), peroxide and determining alcohol Equation, but in individual alcohol, secondary alcohol is easier to aoxidize than primary alconol.However, it was surprisingly found now that by using stabilization The hydrogen peroxide preparation (for example, FMC/PeroxyChem " Super D ") of change mixes in the preparation of the commericially feasible of Xiang Wending low The secondary alcohol 2- propyl alcohol (IPA) of concentration it is really possible.It is further of importance that known primary alconol (such as 1- propyl alcohol) can cause skin red Spot (rubescent) and skin irritatin and the generation of the aldehyde intermediate product decomposed when being applied to skin due to primary alconol, can produce " flare reaction ".Alcohol dehydrogenase present in skin (ADH) acts on primary alconol (such as 1- propyl alcohol) and decomposes primary alconol (such as 1- third Alcohol), but secondary alcohol (such as 2- propyl alcohol) is not acted on.Therefore, only primary alconol (its alcohol dehydrogenase present in skin (ADH) oxygen Turn to corresponding aldehyde) rather than secondary (or uncle) alcohol, cause this erythema to be reacted by this important mechanisms.By by secondary alcohol (such as 2- propyl alcohol) (rather than primary alconol (such as 1- propyl alcohol)) is incorporated into composition, can to avoid or mitigate in the aldehyde being catalyzed by ADH Between product cause or aggravate unfavorable erythema reaction.

Therefore, it was surprisingly found now that the alcohol of low concentration is added into hydrogen peroxide (as retouched in this paper embodiment Those of state alcohol, and especially 2- propyl alcohol) increase the wetabilitys of cutaneous lesions.In addition, cutaneous lesions can for its property To have at crack and/or invagination or surface imperfection that the infiltration of hydrogen peroxide can be made difficult.Therefore, in some embodiment party In case, composition may include hydrogen peroxide and surface tension modifier.In some embodiments, surface tension modifier can Think alcohol.The amount of alcohol, which can be enough for the surface tension of composition to be reduced to, effectively increases composition to as cutaneous lesions The level of crack and/or the infiltration in invagination, the surface area for increasing reaction and increase therapeutic efficiency and/or cutaneous lesions are to treatment The clinical response of property composition.In some embodiments, composition further includes another surface tension modifier.In some realities Apply in scheme, surface tension modifier can be selected from (being not limited to) surfactant, for example, anionic surfactant or it is non-from Sub- surfactant, water soluble surfactant active (such as polysorbate, SLS (lauryl sodium sulfate), polypropylene glycol (PPG) Stearate (such as Arlamol), PEG (polyethylene glycol) stearate, stereth, cetearyl alcohol alcohol ether, polyoxyethylene are hard Resin acid ester etc.), or combinations thereof.The amount of surface tension modifier, which can be enough for the surface tension of composition to be reduced to, to be effectively increased Level that composition is permeated at the crack of cutaneous lesions, invagination and/or surface imperfection, the surface area for increasing reaction and increasing Add therapeutic efficiency and/or cutaneous lesions to the clinical response of therapeutic composition, or combinations thereof.

Particularly, it was surprisingly found now that 2- propyl alcohol is particularly effective in compositions described herein for mixing Alcohol.In fact, it was unexpectedly found that, 2- propyl alcohol is more suitable and more effective than 1- propyl alcohol in compositions described herein Alcohol.1- propyl alcohol allows the release of hydrogen peroxide really, can reduce the surface tension of composition to increase composition to skin Middle infiltration, and it is expected at (being less likely to be oxidized) more stable in the preparation including high-strength hydrogen peroxide.In fact, When compared to 2- propyl alcohol, 1- propyl alcohol provided under some concentration really increased hydrogen peroxide release or increased hydrogen peroxide Rate of release and surface tension (by weight) can be reduced to a greater degree.However, it was surprisingly found now that although It seems possible desired effect, but in the composition of embodiment disclosed herein, and actually 1- propyl alcohol is not as good as 2- The effective alcohol of propyl alcohol.It is not wishing to be bound by theory, it is believed that although (i) tends to the composition containing 1- propyl alcohol to discharge more Hydrogen peroxide, wherein 1- propyl alcohol is but to contain 2- propyl alcohol in embodiments described here under higher concentration Composition effectively discharges hydrogen peroxide and shows more constant rate of release in desired concentration range；(ii) although By weight, 1- propyl alcohol can reduce the surface tension of hydrogen peroxide preparation to a greater degree than 2- propyl alcohol, but preferred real Applying the surface tension reduction induced in the composition of scheme by 1- propyl alcohol is excessive and is suboptimum, because it can be induced So big reduction so that composition will undesirably be spread leaves target lesion or region and spread to non-lesion skin around, until Small part due to undesirable aldehyde intermediate product as discussed above generation and cause detrimental effects (such as stimulation and erythema)； And (iii) although in theory, as discussed, primary alconol (1- propyl alcohol) can be expected in high-strength hydrogen peroxide preparation The stability bigger than secondary alcohol (i.e. 2- propyl alcohol) is shown, but 1- propyl alcohol seems by the high concentration peroxidating of preferred embodiment Hydrogen peroxide oxidation extremely degree more higher than 2- propyl alcohol in hydrogen preparation, and be in fact more unstable.Therefore, herein 2- propyl alcohol is mixed in described composition and provides the remarkable advantage better than incorporation 1- propyl alcohol, and the advantage includes (but unlimited In) improved clinical efficacy, the separate expected applying unit of distribution that the more stable effective preparation-for the treatment of leads to composition are provided The relatively low propensity of position, and therefore more favorable safety.

The amount of alcohol may also be limited by the peroxide concentrations in preparation in composition.Such as, if it is desired to high concentration Peroxide then may must reduce the concentration of alcohol to keep the high concentration of peroxide in preparation.In some embodiments In, the amount of alcohol can be enough to reduce the surface tension of composition, increase composition into the crack of cutaneous lesions and/or invagination Infiltration increases the surface area reacted and increases therapeutic efficiency and/or cutaneous lesions to the clinical response of therapeutic composition.One In a little embodiments, preparation will not undesirably be spread at unaffected non-lesion skin around, this may be due to alcohol Amount is too big or surface tension reduces too many and occurs.In some embodiments, preparation does not stimulate surrounding, non-lesion, not by shadow Loud skin.In some embodiments, preparation does not cause erythema to the unaffected skin of non-lesion around.Surrounding, non-disease Change, the erythema of unaffected skin and stimulation can be caused by generation irritation, the erythema of induction intermediate product (such as aldehyde), This may be attributed to the decomposition of suboptimum alcohol in composition (for example, primary alconol (such as 1- propyl alcohol)).

In some embodiments, composition includes surface tension modifier.In some embodiments, surface tension changes Property agent be alcohol.In some embodiments, the amount of surface tension modifier is enough to reduce the surface of hydrogen peroxide and water formulation Power.In some embodiments, composition includes alcohol, and the amount of the alcohol is enough to reduce the surface of hydrogen peroxide and water formulation Power.In some embodiments, alcohol is primary alconol, secondary alcohol, the tertiary alcohol or combinations thereof.In some embodiments, secondary alcohol is 2- propyl alcohol. In the case where no alcohol (such as 2- propyl alcohol) is to reduce surface tension, hydrogen peroxide-water formulation is likely located on the surface of lesion, And the surface defect of impermeable lesion and/or lesion, irregularity, crack.In some embodiments, surface tension modifier Amount can be enough for the surface tension of composition to be reduced to effectively increase composition to such crack of cutaneous lesions and/or The level of infiltration in invagination, the surface area for increasing reaction increase therapeutic efficiency and/or cutaneous lesions to therapeutic composition Clinical response, while the stimulation of surrounding skin is minimized, or combinations thereof.In addition, excessively reducing the surface of hydrogen peroxide composition The alcohol of tension, which can have to be easy to spread to leave, applies site and the risk across non-lesion skin, causes at required site Compared with low activity and to the destructive stimulus of unaffected skin around and other adverse effects.

In some embodiments, the alcohol in the composition of this paper embodiment can be replaced with other volatility agent.This The volatility agent of sample may include (but being not limited to) volatile matter such as acetic acid esters (for example, ethyl acetate and butyl acetate are (in nail polish The volatile matter used)), cyclomethicone (can be contained in the volatile silicone in emulsifier system) and except shown herein and It is described other than those, it will become apparent to various other volatilizations from the foregoing description to those skilled in the art Object.Such additional volatile agent can be applied in combination with alcohol or alcohol is replaced to use.

In some embodiments, alcohol can selected from primary alconol, secondary alcohol, the tertiary alcohol, or combinations thereof.In some embodiments, Alcohol may include methanol, ethyl alcohol, butanol, 1- propyl alcohol, amylalcohol, hexanol, octanol, nonyl alcohol, decyl alcohol, 2- butanol, 2- propyl alcohol, 2- penta Alcohol, benzylalcohol, its isomers, or combinations thereof.In some embodiments, alcohol is 2- propyl alcohol.Although embodiments herein can be with Specifically mentioned 2- propyl alcohol, it should be appreciated to those skilled in the art that other alcohol and/or volatile matter are (such as (but not limited to) above-mentioned Those) it can replace 2- propyl alcohol and use in such embodiments.

2- propyl alcohol (also referred to as isopropanol (isopropyl alcohol) or isopropanol (isopropanol)) is that have to divide Minor C₃H₈O or C₃H₇The chemical compound of OH.It is colourless, the inflammable chemical compound with overpowering odor.It is secondary alcohol Simplest example, wherein alcohol carbon atom is connected to two other carbon atoms, is shown as (CH sometimes₃)₂CHOH.It is propyl alcohol Constitutional isomer.2- propyl alcohol is miscible with water, alcohol, ether and chloroform.It is by ethyl cellulose dissolved, polyvinyl alcohol contracting fourth Aldehyde, much oil, alkaloid, natural gum and natural resin.It does not dissolve in salting liquid.Different from ethyl alcohol or methanol, 2- propyl alcohol can lead to It crosses addition salt (such as sodium chloride, sodium sulphate or any other several inorganic salts) to separate from aqueous solution, because alcohol is in saline solution It is middle than in salt-free water solubility it is much lower.2- propyl alcohol has many medical usages and medicinal usage and Yu Shuizhong is about Under the concentration of 60% to about 70% usually part be used as partly sterilised's agent and in gel about 60% to about 75%v/v concentration It is used as hand cleanser down.2- propyl alcohol is also used as under up to 95% concentration for treating/preventing otitis externa (swim ear) Water drying aids.

In some embodiments, the amount of alcohol is up to the about 0.1%w/w of composition, is up to about 0.25%w/w, is up to about 0.5%w/w, be up to about 1%w/w, be up to about 2%w/w, be up to about 2.5%w/w, be up to about 3%w/w, be up to about 4%w/w, It is up to about 5%w/w, 8%w/w is up to about, is up to about 10%w/w, is up to about 14%w/w, is up to about 15%w/w, is up to about 20%w/w or up to about 25%w/w.As described in this paper embodiment, the alcohol (for example, 2- propyl alcohol) of low concentration is used Allow the stabilized hydrogen peroxide (such as from about 23% or higher hydrogen peroxide) using treatment high concentration, so that in hydrogen peroxide Stabilizer be able to maintain that the chemical stability of preparation, without being influenced by alcohol (and its impurity).In some embodiments, alcohol Composition can be accounted for is up to about 25%w/w.In some embodiments, the amount of alcohol can be about 0.05%w/w to about 25% W/w, about 0.5%w/w are to about 25%w/w, about 1%w/w to about 25%w/w, about 2.5%w/w to about 25%w/w, about 5%w/w To about 25%w/w, about 10%w/w to about 25%w/w, about 15%w/w to about 25%w/w or about 20%w/w to about 25%w/w, About 0.05%w/w to about 15%w/w, about 0.5%w/w to about 25%w/w, be up to about 5%w/w, about 0.01%w/w to about 5% W/w, about 0.1%w/w to about 5%w/w, about 0.5%w/w to about 5%w/w, about 1%w/w to about 5%w/w, about 1.5%w/w extremely About 5%w/w, about 2%w/w are to about 5%w/w, about 2.5%w/w to about 5%w/w, about 3%w/w to about 5%w/w, about 3.5%w/ W to about 5%w/w, about 4%w/w are to about 5%w/w, about 4.5%w/w to about 5%w/w, etc..In some embodiments, alcohol Amount can be about 0.01%w/w, about 0.1%w/w, about 0.25%w/w, 0.5%w/w, about 0.75%w/w, about 1%w/w, about 2%w/w, about 2.5%w/w, about 3%w/w, about 4%w/w, about 5%w/w, about 10%w/w, about 15%w/w, about 20%w/w, about The range of any two in 25%w/w or these values.

In some embodiments, composition includes the alcohol of the hydrogen peroxide and up to about 10%w/w greater than 40%w/w. In some embodiments, composition includes the alcohol of the up to about hydrogen peroxide of 70%w/w and up to about 10%w/w.Some In embodiment, composition includes the alcohol of the up to about hydrogen peroxide of 60%w/w and up to about 10%w/w.In some embodiment party In case, composition includes the alcohol of the hydrogen peroxide and up to about 10%w/w greater than 40%w/w to about 60%w/w.In some implementations In scheme, composition includes the alcohol of the up to about hydrogen peroxide of 50%w/w and up to about 10%w/w.In some embodiments, Composition includes the alcohol of the hydrogen peroxide and up to about 10%w/w greater than 40%w/w to about 50%w/w.In some embodiments In, composition includes the hydrogen peroxide of about 40%w/w and the alcohol of about 10%w/w.In some embodiments, composition includes about The alcohol of the hydrogen peroxide of 41%w/w and up to about 10%w/w.In some embodiments, composition includes the mistake of about 42%w/w The alcohol of hydrogen oxide and up to about 10%w/w.In some embodiments, composition includes the hydrogen peroxide of about 43%w/w and more Alcohol of about 10%w/w.In some embodiments, composition includes the hydrogen peroxide and up to about 10%w/w of about 44%w/w Alcohol.In some embodiments, composition includes the hydrogen peroxide of about 45%w/w and the alcohol of up to about 10%w/w.Some In embodiment, composition includes the hydrogen peroxide of about 46%w/w and the alcohol of up to about 10%w/w.In some embodiments, Composition includes the hydrogen peroxide of about 47%w/w and the alcohol of up to about 10%w/w.In some embodiments, composition includes The alcohol of the hydrogen peroxide of about 48%w/w and up to about 10%w/w.In some embodiments, composition includes about 49%w/w The alcohol of hydrogen peroxide and up to about 10%w/w.In some embodiments, composition includes the up to about peroxidating of 50%w/w The alcohol of hydrogen and 10%w/w.In some embodiments, composition includes the up to about hydrogen peroxide of 50%w/w and up to about 5% The alcohol of w/w.In some embodiments, composition includes the alcohol of the up to about hydrogen peroxide of 60%w/w and 10%w/w.One In a little embodiments, composition includes the alcohol of the up to about hydrogen peroxide of 60%w/w and up to about 5%w/w.In some embodiment party In case, composition includes the alcohol of the up to about hydrogen peroxide of 55%w/w and 10%w/w.In some embodiments, composition packet Include the alcohol of the up to about hydrogen peroxide of 55%w/w and up to about 5%w/w.In some embodiments, composition includes being greater than The alcohol of the hydrogen peroxide of 40%w/w and up to about 5%w/w.In some embodiments, composition includes being greater than 40%w/w extremely The alcohol of the hydrogen peroxide of about 60%w/w and up to about 5%w/w.In some embodiments, composition includes about 40%w/w The alcohol of hydrogen peroxide and about 5%w/w.In some embodiments, composition includes the hydrogen peroxide and up to about of about 41%w/w The alcohol of 5%w/w.In some embodiments, composition includes the hydrogen peroxide of about 42%w/w and the alcohol of up to about 5%w/w. In some embodiments, composition includes the hydrogen peroxide of about 43%w/w and the alcohol of up to about 5%w/w.In some embodiment party In case, composition includes the hydrogen peroxide of about 44%w/w and the alcohol of up to about 5%w/w.In some embodiments, composition The alcohol of hydrogen peroxide and up to about 5%w/w including about 45%w/w.In some embodiments, composition includes about 46%w/ The alcohol of the hydrogen peroxide of w and up to about 5%w/w.In some embodiments, composition includes the hydrogen peroxide of about 47%w/w The up to about alcohol of 5%w/w.In some embodiments, composition includes the hydrogen peroxide and up to about 5% of about 48%w/w The alcohol of w/w.In some embodiments, composition includes the hydrogen peroxide of about 49%w/w and the alcohol of up to about 5%w/w.One In a little embodiments, composition includes the hydrogen peroxide of about 50%w/w and the alcohol of 5%w/w.In some embodiments, it combines Object includes the hydrogen peroxide of about 60%w/w and the alcohol of 5%w/w.In some embodiments, composition includes up to about 60%w/ The alcohol of the hydrogen peroxide of w and up to about 2.5%w/w.In some embodiments, composition includes the peroxidating of about 50%w/w The alcohol of hydrogen and up to about 2.5%w/w.In some embodiments, composition includes the hydrogen peroxide and up to greater than 40%w/w The alcohol of about 2.5%w/w.In some embodiments, composition include greater than 40%w/w to about 60%w/w hydrogen peroxide and The up to about alcohol of 2.5%w/w.In some embodiments, composition includes the hydrogen peroxide and about 2.5%w/w of about 40%w/w Alcohol.In some embodiments, composition includes the hydrogen peroxide of about 41%w/w and the alcohol of up to about 2.5%w/w.One In a little embodiments, composition includes the hydrogen peroxide of about 42%w/w and the alcohol of up to about 2.5%w/w.In some embodiments In, composition includes the hydrogen peroxide of about 43%w/w and the alcohol of up to about 2.5%w/w.In some embodiments, composition The alcohol of hydrogen peroxide and up to about 2.5%w/w including about 44%w/w.In some embodiments, composition includes about 45% The alcohol of the hydrogen peroxide of w/w and up to about 2.5%w/w.In some embodiments, composition includes the peroxide of about 46%w/w Change the alcohol of hydrogen and up to about 2.5%w/w.In some embodiments, composition includes the hydrogen peroxide and up to of about 47%w/w The alcohol of about 2.5%w/w.In some embodiments, composition includes the hydrogen peroxide and up to about 2.5%w/w of about 48%w/w Alcohol.In some embodiments, composition includes the hydrogen peroxide of about 49%w/w and the alcohol of up to about 2.5%w/w.One In a little embodiments, composition includes the alcohol of the up to about hydrogen peroxide of 50%w/w and 2.5%w/w.In some embodiments In, composition includes the hydrogen peroxide of about 60%w/w and the alcohol of 2.5%w/w.In some embodiments, composition includes big In the hydrogen peroxide of 40%w/w and the alcohol of up to about 2%w/w.In some embodiments, composition includes being greater than 40%w/w To the hydrogen peroxide of about 60%w/w and the alcohol of up to about 2%w/w.In some embodiments, composition includes about 40%w/w Hydrogen peroxide and about 2%w/w alcohol.In some embodiments, composition includes the hydrogen peroxide and up to of about 41%w/w The alcohol of about 2%w/w.In some embodiments, composition includes the hydrogen peroxide and up to about 2%w/w of about 42%w/w Alcohol.In some embodiments, composition includes the hydrogen peroxide of about 43%w/w and the alcohol of up to about 2%w/w.In some realities It applies in scheme, composition includes the hydrogen peroxide of about 44%w/w and the alcohol of up to about 2%w/w.In some embodiments, group Closing object includes the hydrogen peroxide of about 45%w/w and the alcohol of up to about 2%w/w.In some embodiments, composition includes about The alcohol of the hydrogen peroxide of 46%w/w and up to about 2%w/w.In some embodiments, composition includes the mistake of about 47%w/w The alcohol of hydrogen oxide and up to about 2%w/w.In some embodiments, composition includes the hydrogen peroxide and up to of about 48%w/w The alcohol of about 2%w/w.In some embodiments, composition includes the hydrogen peroxide and up to about 2%w/w of about 49%w/w Alcohol.In some embodiments, composition includes the alcohol of the up to about hydrogen peroxide of 50%w/w and 2%w/w.In some implementations In scheme, composition includes the hydrogen peroxide of about 60%w/w and the alcohol of 2%w/w.In some embodiments, composition includes The up to about alcohol of the hydrogen peroxide of 60%w/w and 2%w/w.In some embodiments, alcohol is 2- propyl alcohol.

In some embodiments, composition is substantially made of the up to about hydrogen peroxide of 60%w/w.In some implementations In scheme, composition is substantially made of the hydrogen peroxide greater than 40%w/w.In some embodiments, composition is substantially It is made of the hydrogen peroxide greater than 40%w/w to about 60%w/w.In some embodiments, composition is substantially by up to about The hydrogen peroxide of 50%w/w forms.In some embodiments, composition is substantially made of the hydrogen peroxide of about 59%w/w. In some embodiments, composition is substantially made of the hydrogen peroxide of about 55%w/w.In some embodiments, it combines Object is substantially made of the hydrogen peroxide of about 54%w/w.In some embodiments, composition is substantially by about 50%w/w's Hydrogen peroxide composition.In some embodiments, composition is substantially made of the hydrogen peroxide of about 45%w/w.In some realities It applies in scheme, composition is substantially made of the up to about hydrogen peroxide of 60%w/w and alcohol.In some embodiments, it combines Object is substantially made of the hydrogen peroxide and alcohol that are greater than 40%w/w.In some embodiments, composition is substantially by being greater than The alcohol of 40%w/w and up to about 5%w/w form.In some embodiments, composition is substantially by being greater than 40%w/w to about The alcohol of the hydrogen peroxide of 60%w/w and up to about 5%w/w form.In some embodiments, composition is substantially by about 41% The alcohol of the hydrogen peroxide of w/w and up to about 5%w/w form.In some embodiments, composition is substantially by about 42%w/w Hydrogen peroxide and up to about 5%w/w alcohol composition.In some embodiments, composition is substantially by the mistake of about 43%w/w The alcohol of hydrogen oxide and up to about 5%w/w form.In some embodiments, composition is substantially by the peroxidating of about 44%w/w The alcohol of hydrogen and up to about 5%w/w form.In some embodiments, composition substantially by the hydrogen peroxide of about 45%w/w and The alcohol of up to about 5%w/w forms.In some embodiments, composition is substantially by the hydrogen peroxide of about 46%w/w and up to The alcohol of about 5%w/w forms.In some embodiments, composition is substantially by the hydrogen peroxide of about 47%w/w and up to about The alcohol of 5%w/w forms.In some embodiments, composition is substantially by the hydrogen peroxide of about 48%w/w and up to about 5% The alcohol of w/w forms.In some embodiments, composition is substantially by the hydrogen peroxide of about 49%w/w and up to about 5%w/w Alcohol composition.In some embodiments, composition is substantially made of the up to about hydrogen peroxide of 50%w/w and alcohol.One In a little embodiments, composition is substantially made of the alcohol of the hydrogen peroxide of about 40%w/w and about 5%w/w.In some embodiment party In case, composition is substantially made of the alcohol of the hydrogen peroxide of about 35%w/w and about 5%w/w.In some embodiments, group Object is closed substantially to be made of the alcohol of the hydrogen peroxide of about 32.5%w/w and about 5%w/w.In some embodiments, composition base It is made of in sheet the alcohol of the hydrogen peroxide of about 25%w/w and about 5%w/w.In some embodiments, composition is substantially by more Hydrogen peroxide and alcohol composition of about 60%w/w.In some embodiments, composition is substantially by the peroxide of about 59%w/w Change hydrogen and the alcohol composition of about 5%w/w.In some embodiments, composition is substantially by the hydrogen peroxide peace treaty of about 55%w/w The alcohol of 5%w/w forms.In some embodiments, composition is substantially by the hydrogen peroxide of about 54%w/w and about 5%w/w Alcohol composition.In some embodiments, composition is substantially made of the alcohol of the hydrogen peroxide of about 50%w/w and about 5%w/w. In some embodiments, composition is substantially made of the alcohol of the hydrogen peroxide of about 45%w/w and about 5%w/w.

In some embodiments, composition is made of the up to about hydrogen peroxide of 60%w/w.In some embodiments In, composition is made of the up to about hydrogen peroxide of 50%w/w.In some embodiments, composition is by greater than 40%w/w's Hydrogen peroxide composition.In some embodiments, composition is made of the hydrogen peroxide greater than 40%w/w to about 60%w/w.? In some embodiments, composition is made of the hydrogen peroxide of about 45%w/w.In some embodiments, composition is by up to The hydrogen peroxide and alcohol of about 60%w/w forms.In some embodiments, composition is by the up to about hydrogen peroxide of 50%w/w It is formed with alcohol.In some embodiments, composition is by being greater than the hydrogen peroxide of 40%w/w and the alcohol group of up to about 5%w/w At.In some embodiments, composition is by the hydrogen peroxide and up to about 5%w/w greater than 40%w/w to about 60%w/w Alcohol composition.In some embodiments, composition is made of the hydrogen peroxide of about 41%w/w and the alcohol of up to about 5%w/w.? In some embodiments, composition is made of the hydrogen peroxide of about 42%w/w and the alcohol of up to about 5%w/w.In some embodiment party In case, composition is made of the hydrogen peroxide of about 43%w/w and the alcohol of up to about 5%w/w.In some embodiments, it combines Object is made of the hydrogen peroxide of about 44%w/w and the alcohol of up to about 5%w/w.In some embodiments, composition is by about 45% The alcohol of the hydrogen peroxide of w/w and up to about 5%w/w form.In some embodiments, composition by about 46%w/w peroxide Change hydrogen and the alcohol composition of up to about 5%w/w.In some embodiments, composition by about 47%w/w hydrogen peroxide and up to The alcohol of about 5%w/w forms.In some embodiments, composition by about 48%w/w hydrogen peroxide and up to about 5%w/w Alcohol composition.In some embodiments, composition is made of the hydrogen peroxide of about 49%w/w and the alcohol of up to about 5%w/w.? In some embodiments, composition is made of the up to about hydrogen peroxide of 50%w/w and alcohol.In some embodiments, it combines Object is made of the hydrogen peroxide of about 40%w/w and the alcohol of about 5%w/w.In some embodiments, composition is by about 35%w/w Hydrogen peroxide and about 5%w/w alcohol composition.In some embodiments, composition by about 32.5%w/w hydrogen peroxide and The alcohol of about 5%w/w forms.In some embodiments, composition is by the hydrogen peroxide of about 25%w/w and the alcohol group of about 5%w/w At.In some embodiments, composition is made of the up to about hydrogen peroxide of 60%w/w and alcohol.In some embodiments, Composition is made of the hydrogen peroxide of about 59%w/w and the alcohol of about 5%w/w.In some embodiments, composition is by about 55% The alcohol of the hydrogen peroxide of w/w and about 5%w/w form.In some embodiments, composition by about 54%w/w hydrogen peroxide The alcohol of about 5%w/w forms.In some embodiments, composition is by the hydrogen peroxide of about 50%w/w and the alcohol of about 5%w/w Composition.In some embodiments, composition is made of the hydrogen peroxide of about 45%w/w and the alcohol of about 5%w/w.In some realities It applies in scheme, alcohol is 2- propyl alcohol.

In some embodiments, alcohol reduces the surface tension of composition.In some embodiments, alcohol increases peroxidating Infiltration of the hydrogen in (irregularity, crack and the defect of such as skin or cutaneous lesions) at the skin defect of subject.Some In embodiment, alcohol makes the skin of subject or the cutaneous lesions degreasing of subject, to allow hydrogen peroxide to subject's Better infiltration in skin or cutaneous lesions.In some embodiments, the wetability that alcohol increases skin surface (includes skin The wetability of growth or cutaneous lesions).In some embodiments, the amount of 2- propyl alcohol is enough to reduce the surface tension of composition. In some embodiments, the amount of 2- propyl alcohol is enough to reduce the surface tension of composition, is enough to enhance composition to target skin Infiltration in region or target cutaneous lesions.In some embodiments, the amount of surface tension modifier is enough to enhance composition Therapeutic efficiency.

In some embodiments, the effective concentration of hydrogen peroxide when alcohol increases application.Hydrogen peroxide is sterilization, kills disease It is poison, sporicidal and antifungal, and can be the fungicide in various concentration and time of contact.In some embodiments In, the concentration of hydrogen peroxide is enough to kill the virus.In some embodiments, hydrogen peroxide has with skin or cutaneous lesions Enough times of contact show its bactericidal effect, the effect of killing the virus for it, kill spore effect, fungicidal action or fungicide work With.In some embodiments, hydrogen peroxide and skin or cutaneous lesions have enough times of contact so that disease is killed in its performance Toxic action.Without being bound by theory, alcohol can increase effective concentration when hydrogen peroxide evaporates after application, and can increase system The oxidation activity and/or bactericidal activity of agent.In addition, the increased infiltration of preparation can increase solution and skin or cutaneous lesions Surface area or time of contact, and lead to the effect of the enhancing as fungicide (germicide) or fungicide (sterilant) Fruit.In addition, and it is without being bound by theory, increased penetration depth and/or contact surface area can induce or increase local immunity Response or general immunity response, the local immune response or general immunity response can supplement above-mentioned therapeutic effect and cause The target verrucous lesion being not only treated, but also it is located remotely from other non-target warts at the site in treated target wart site more Quickly or more effectively remove.

In some embodiments, composition can be applied topically.In some embodiments, composition can be molten Liquid.In some embodiments, composition can be in gel preparation.In some embodiments, solution or gel preparation can be with In in application or in preceding two or more the mixed parts of application immediately.In some embodiments, composition can be with In creme, lotion, ointment, foam, transdermal skin patches, pulvis, solid, band, paste or tincture.In some embodiments, herein Treatment method described in embodiment only needs the primary single application of the composition of this paper embodiment.In some implementations In scheme, treatment method described in this paper embodiment needs applying two or more times for the composition of this paper embodiment Add.In some embodiments, treatment method described in this paper embodiment needs the composition of this paper embodiment Multiple application.

In some embodiments, composition can also include pharmaceutically acceptable excipient.In some embodiments In, composition also with comprising lubricant, emulsifier, gelling agent, additive, or combinations thereof.In some embodiments, additive Preservative, emulsion stabilizer, pH adjusting agent, chelating agent, viscosity modifier, antioxidant, surfactant, washing can be selected from Agent, lubricant, opacifier, skin conditioning agent, buffer, or combinations thereof.

Some embodiments of this paper be related to include hydrogen peroxide and gelling agent gel preparation.In some embodiments In, gel preparation can also include alcohol.In some embodiments, gel preparation can also include pharmaceutically acceptable figuration Agent.In some embodiments, gelling agent can be selected from carbopol (Carbopol) ETD 2020, carbopol 980NF, carbopol 974P, carbopol Ultrez 10 etc..In some embodiments, gelling agent can be high molecular weight, the copolymerzation with cross-linking of acrylic acid Object and hydrophobic comonomer or copolymer (for example, Pemulen TR-1)；Polycarbophil AA-1 (Polycarbophil AA-1)； PVP (polyvinylpyrrolidone)；Utech (Eudragit)；Poloxamer (Poloxamer)；Sepineo；Bentonite； Aerosil (silicate)；Hyaluronic acid；Cross-linked-hyaluronic acid；A combination thereof or its group with embodiments described here Close the composition or chemical equivalent of characteristic required for object.In some embodiments, gel combination keeps being in two portions Divide and is mixed when applying or before applying immediately.For example, hydrogen peroxide and 2- propyl alcohol (first part) is able to maintain and glue Solidifying agent (second part) separation, until application or application immediately.As another example, hydrogen peroxide, 2- propyl alcohol and glue Solidifying agent can respectively be divided into three parts and the mixing when applying or before applying immediately.Extention can be assigned for additional Shape agent is that possible or such excipient can be impregnated in existing part.It, can be with before applying in application or immediately It mixes more partial gel preparations and is locally applied to skin as single gel preparation.

Some embodiments are related to the gel preparation that can be delivered in applicator, and the applicator is when applying or vertical Two or more components of mixed gel preparation before applying.In some embodiments, gel preparation compartment applicator Including at least one frangible compartment, (for example, gelling agent is in the main compartment of applicator, wherein hydrogen peroxide is in the compartment It is interior or in the glass ampule beside the compartment).Some exemplary applicators may include syringe-like applicator or " two-tube " Applicator can newly be mixed (for example, " vortex mixed ") and be needed to be maintained in independent compartment due to stability reasons, but Two or more components that can be mixed when applying or before applying immediately.

In some embodiments, composition also includes buffer.In some embodiments, buffer can be selected from three Ethanol amine, low pH buffer are (such as sodium acetate, citrate, phosphate, glycine, hydrogen chloride, citrate and phosphate, sweet Propylhomoserin and hydrogen chloride etc.), or combinations thereof.In some embodiments, buffer can be with about 0.001%w/w to about 15%w/w Amount exist.In some embodiments, buffer with about 0.001%w/w, 0.01%w/w, 0.05%w/w, 0.1%w/w, The amount of the range of any two exists in 0.5%w/w, 1%w/w, 5%w/w, 10%w/w, 15%w/w or these values.One In a little embodiments, buffer exists with any amount necessary to the pH of most preferably regulation composition.

In some embodiments, composition has the surface tension of about 15mNm-1 to about 80mNm-1 in room temperature. In some embodiments, composition has about 20mNm-1 to about 80mNm-1, about 30mNm-1 to about at 37 DEG C 80mNm-1, about 40mNm-1 are to about 80mNm-1, about 50mNm-1 to about 80mNm-1, about 35mNm-1 to about 80mNm-1, about 35mNm-1 are to about 70mNm-1, about 35mNm-1 to about 60mNm-1, about 35mNm-1 to about The surface tension of 50mNm-1 has about 40mNm-1 to about 80mNm-1, about 40mNm-1 to about 70mN in room temperature M-1, about 40mNm-1 are to about 60mNm-1, about 40mNm-1 to about 50mNm-1, about 45mNm-1 to about 80mNm- 1, about 45mNm-1 to about 70mNm-1, about 45mNm-1 are to about 60mNm-1 or about 45mNm-1 to about 50mNm- 1 surface tension.In some embodiments, composition has about 15mNm-1, about 20mNm-1, about 30mN in room temperature M-1, about 36mNm-1, about 41mNm-1, about 48mNm-1, about 54mNm-1, about 75mNm-1, about 40mNm-1, The table of the range of any two in about 50mNm-1, about 60mNm-1, about 70mNm-1, about 80mNm-1 or these values Face tension.In some embodiments, composition has the surface tension of about 42mNm-1 to about 55mNm-1 in room temperature.? In some embodiments, composition has the surface tension of about 42mNm-1 to about 50mNm-1 in room temperature.

In some embodiments, composition is in 37 DEG C of surface tension with about 15mNm-1 to about 80mNm-1. In some embodiments, composition has about 20mNm-1 to about 80mNm-1, about 30mNm-1 to about at 37 DEG C 80mNm-1, about 40mNm-1 are to about 80mNm-1, about 50mNm-1 to about 80mNm-1, about 35mNm-1 to about 80mNm-1, about 35mNm-1 are to about 70mNm-1, about 35mNm-1 to about 60mNm-1, about 35mNm-1 to about The surface tension of 50mNm-1 has about 40mNm-1 to about 80mNm-1, about 40mNm-1 to about 70mN at 37 DEG C M-1, about 40mNm-1 are to about 60mNm-1, about 40mNm-1 to about 50mNm-1, about 45mNm-1 to about 80mNm- 1, about 45mNm-1 to about 70mNm-1, about 45mNm-1 are to about 60mNm-1 or about 45mNm-1 to about 50mNm- 1 surface tension.In some embodiments, composition has about 15mNm-1, about 20mNm-1, about 30mN at 37 DEG C M-1, about 36mNm-1, about 41mNm-1, about 48mNm-1, about 54mNm-1, about 75mNm-1, about 40mNm-1, The table of the range of any two in about 50mNm-1, about 60mNm-1, about 70mNm-1, about 80mNm-1 or these values Face tension.In some embodiments, composition is in 37 DEG C of surface tension with about 42mNm-1 to about 55mNm-1.? In some embodiments, composition is in 37 DEG C of surface tension with about 42mNm-1 to about 50mNm-1.

In some embodiments, the composition including the hydrogen peroxide greater than 40%w/w has at 37 DEG C from about The surface tension of 35mNm-1 to about 60.3mNm-1.In some embodiments, including the hydrogen peroxide greater than 40%w/w Composition can have the surface tension of about 60.3mNm-1 at 37 DEG C.Including greater than 40%w/w hydrogen peroxide and The composition of the 2- propyl alcohol of 2.5%w/w can have about 54.1+/- 0.8mNm-1 surface tension at 37 DEG C.Including being greater than The composition of the 2- propyl alcohol of the hydrogen peroxide and 5%w/w of 40%w/w can have about 48.3+/- 0.7mNm-1 at 37 DEG C Surface tension.The composition of 2- propyl alcohol including hydrogen peroxide and 10%w/w greater than 40%w/w can have about at 37 DEG C 41.1+/- 0.6mNm-1 surface tension.The combination of 2- propyl alcohol including hydrogen peroxide and 15%w/w greater than 40%w/w Object can have about 35.9+/- 0.6mNm-1 surface tension at 37 DEG C.

In some embodiments, the composition of the hydrogen peroxide including about 45%w/w has at 37 DEG C from about 35mN The surface tension of m-1 to about 60.3mNm-1.In some embodiments, the composition of the hydrogen peroxide including about 45%w/w It can have the surface tension of about 60.3mNm-1 at 37 DEG C.The 2- third of hydrogen peroxide and 2.5%w/w including about 45%w/w The composition of alcohol can have about 54.1+/- 0.8mNm-1 surface tension at 37 DEG C.Hydrogen peroxide including about 45%w/w It can have about 48.3+/- 0.7mNm-1 surface tension at 37 DEG C with the composition of the 2- propyl alcohol of 5%w/w.Including about The composition of the 2- propyl alcohol of the hydrogen peroxide and 10%w/w of 45%w/w can have about 41.1+/- 0.6mNm-1 at 37 DEG C Surface tension.The composition of the 2- propyl alcohol of hydrogen peroxide and 15%w/w including about 45%w/w can have about 35.9 at 37 DEG C The surface tension of +/- 0.6mNm-1.

In some embodiments, composition has the pH of about 1.5 to about 7.0.In some embodiments, pH can be About 1.5 to about 3.5, about 1.5 to about 5.0, about 1.5 to about 4.0, about 1.7 to about 3.7, about 2.0 to about 5.0, about 2.0 to about 4.0, about 2.0 to about 2.8, about 2.5 to about 4.0, about 2.5 to about 4.5, about 2.5 to about 5.0, about 2.7 to about 3.83, about 2.7 to About 4.0, about 2.8 to about 4.0, about 2.83 to about 3.83, about 3.0 to about 7.0, about 4.0 to about 7.0, about 5.0 to about 7.0 or about 6.0 to about 7.0.In some embodiments, pH can be about 1.5,1.7,2.0,2.5,2.7,2.8,2.83,3.0,3.3, 3.5,3.7,3.83,4.0,4.5,5.0,5.5,6.0,6.5,7.0 or these values in any two range.

In some embodiments, the composition of this paper embodiment is long of about surrounding in ambient-temp-stable.In some implementations In scheme, the composition of this paper embodiment ambient-temp-stable it is long of about 15 minutes, about 30 minutes, about 1 hour, about 2 hours, about 3 hours, about 4 hours, about 5 hours, about 6 hours, it is long of about 12 hours, it is long of about 24 hours, it is long of about 1 week, it is long of about 2 weeks, It is long of about 3 weeks, it is long of about 1 month, it is long of about 6 weeks, it is long of about 2 months, it is long of about 3 months, length of about 4 months, length of about 6 Month, it is long of about 8 months, it is long of about 10 months, it is long of about 12 months, it is long of about 18 months, it is long of about 2 years, it is long of about 2.5 years, Or it is long of about 3 years.In some embodiments, the composition of this paper embodiment be stable for up at 40 DEG C about surrounding, it is long of about Six weeks, it is long of about eight weeks, it is long of about three months, it is long of about 6 months, it is long of about 8 months or length was of about 1 year.In some implementations In scheme, the composition of this paper embodiment be stable for up at 30 DEG C about surrounding, it is long of about 6 weeks, it is long of about 1 month, grow of about 2 A month, it is long of about 3 months, it is long of about 4 months, it is long of about 6 months, it is long of about 8 months, it is long of about 10 months, it is long of about 12 The moon, length are of about 2.5 years or long of about 3 years of about 2 years, length of about 18 months, length.In some embodiments, this paper embodiment party The composition of case be stable for up at 25 DEG C about surrounding, it is long of about 1 month, it is long of about 6 weeks, it is long of about 2 months, it is long of about 3 months, It is long of about 4 months, it is long of about 6 months, it is long of about 8 months, it is long of about 10 months, it is long of about 12 months, it is long of about 18 months, it is long It is of about 2.5 years or long of about 3 years of about 2 years, length.In some embodiments, the composition of this paper embodiment is steady at 5 DEG C Fixed length of about surrounding, it is long of about 6 weeks, it is long of about 1 month, it is long of about 2 months, it is long of about 3 months, it is long of about 4 months, length of about 6 months, it is long of about 8 months, it is long of about 10 months, it is long of about 12 months, it is long of about 18 months, it is long of about 2 years, it is long of about 2.5 Year is long of about 3 years.E.g., including the composition of the 2- propyl alcohol of the hydrogen peroxide of about 40%w/w and about 5%w/w at 5 DEG C and 25 DEG C are stablized 9 months, and are stablized 6 months at 40 DEG C.As another example, hydrogen peroxide and 5%w/ including about 45%w/w The composition of the 2- propyl alcohol of w is stablized 12 months in 5 DEG C and 25 DEG C, and stablizes 6 months at 40 DEG C.

In some embodiments, the composition of this paper embodiment meets by the date is on 2 6th, 2003 existing the 4 step versions, " ICH Harmonised Tripartite Guideline:Stability Testing of New Drug International Conference of Harmonisation in Substances and Products Q1A (R2) " of Technical Requirements for Registration of Pharmaceuticals for Human Use The stability requirement that (it is integrally incorporated herein by reference) proposes.

In some embodiments, the composition of this paper embodiment can also with mechanically, physically or chemically increase Strongly active dose of infiltration into lesion or can enhance in another way composition therapeutic efficiency other methods combination Application.Such method may include adhesive tape removing, destructiveness/ablative mode, e.g., for example, cold therapy, electrosurgery, scraping Except the application (for example, salicylic acid, trichloroacetic acid) of art, laser therapy, acid；Localized cytotoxicity therapy, it is such as local with Podophyllum emodi var chinense tree 5 FU 5 fluorouracil or bleomycin in rouge, cantharidin or part or lesion；Immunosuppressant therapy therapy is (for example, part miaow Quinoline is special, candida antigens in lesion, part use side dibutyl phthalate, takes orally Cimetidine) or surgery lesion remove, electric seasoning Method, the laser (ablative and non-ablative) of various wavelength, RF ablation, dermabrasion and pass through curettage or operation excision Partially or completely operation removal, use ablation agent chemical strippers or in another way upset lesion surface or reduce The thickness or size or total volume of lesion or the surface area for increasing lesion.In some embodiments, the group of this paper embodiment Closing object can be administered in combination with other active components (e.g., for example, adjuvant, inhibitor or other biocompatible pharmaceuticals or compound), Wherein such combination is considered in the desired effect for realizing approach described herein being desired or advantageous.It is any Other known treatment can also be used with formulation compositions, to treat skin disease disclosed herein.For example, composition can be with Active agents for treating the patient's condition described herein are administered in combination.In some embodiments, the group of this paper embodiment Another compound can applied with before treating lesion, simultaneously or later apply by closing object.In some embodiments, it combines Object further includes the Topically active medicament for treating the patient's condition described herein.As example, the method for treating wart may include Salicylic acid is applied to the lesion of people in need in the morning and applies this paper embodiment party to the lesion of people in need at night The composition of case.Another example includes the method for the treatment of wart, cold the method includes applying in health care environment to lesion Freeze therapy or local failure sex therapy, is followed by the routine (example of one of a kind of or a series of compositions described hereins Such as, daily or weekly) apply.As another example, the method for treating wart, condyloma acuminatum or molluscum may include in need People the lesion application part many days of vitamin A acid and pre-processing the rear in need of many days with local application's agent The lesion of people applies the composition of this paper embodiment.Other possible examples will be apparent for those skilled in the art 's.Other activating agents or process can be applied or be carried out before, after or at the same time in the composition of this paper embodiment.

Embodiments herein further relates to the method that wart or wart related conditions are treated in subject in need, the side Method includes that the composition of this paper embodiment is applied to subject in need.In some embodiments, composition can be by Once a day, twice daily, once a week, twice a week, three-times-weekly, it is every other day primary, monthly, the every two moon one Secondary, every three months once or by packaging or doctor instructs application, to realize desired clinical effectiveness.In some embodiments, Composition is applied once a week.In some embodiments, composition is administered twice weekly.In some embodiments, Composition is administered once or is administered at regular intervals one week, two weeks, three weeks, surrounding, five weeks, six weeks, seven weeks, eight Week, nine weeks, ten weeks, 11 weeks, 12 weeks, one month, two months, three months, four months, five months, six months or these values In any two range.In some embodiments, composition be administered at least about one week, at least about two weeks, at least about Three weeks, at least about surrounding, at least about five weeks, at least about six weeks, at least about seven weeks, at least about eight weeks, at least about nine weeks, at least about Ten weeks, at least about 11 weeks, at least about 12 weeks, at least about one month, at least about two months, at least about three months, at least about Four months, at least about five months, at least about six months, the range of any two in these values or until lesion subsides.One In a little embodiments, composition is administered until lesion subsides.In some embodiments, composition can be applied once a week With eight weeks.In some embodiments, composition can be administered eight weeks twice a week.In some embodiments, composition It can be administered one week, and be then administered once a week or twice a week until lesion subsides once a day.Any other The combination of quantity is possible, and those skilled in the art will be apparent.

The patient's condition can be spreading venereal diseases because.In some embodiments, the patient's condition can be selected from human papilloma virus induction Lesion is (for example, under wart, verruca vulgaris, recurrent wart, verruca filiformis, genital wart, external genital organs wart, duration wart, periungual wart, first Wart, mosaic warts, intractable wart, just controls wart, palmoplantar verruca, verruca plana, epidermodysplasia verruciformis correlation wart, anus reproduction at plantar wart Device wart, condyloma acuminatum, cervical atypical hyperplasia or tumor-like lesion (for example, cervical intraepithelial neoplasia (CIN) (CIN))；Poxvirus The lesion (for example, molluscum contagiosum (molluscum acne), oof (secondary acne)) of (Poxviridae) induction, or combinations thereof.In some realities It applies in scheme, subject realizes that the improvement of cutaneous lesions or part are removed after being treated with composition.In some embodiments In, subject realizes the fully erased of cutaneous lesions during being treated with composition.In some embodiments, subject The fully erased of cutaneous lesions is realized after the process treated with composition.In some embodiments, lesion was being treated Continue to improve after journey and/or subside.In some embodiments, subject may be implemented to around treatment site or distant place The improvement of the patient's condition and/or lesion is fully erased.It is not wishing to be bound by theory, it is believed that can be induced pair with confectionery composition treatment Cause local immune response or the general immunity response of the virus of the patient's condition.

In some embodiments, treating wart or the method for wart related conditions further includes cleaning to control before applying composition The step for the treatment of site.In some embodiments, the operation for cleaning treatment site, which is included in application composition, to be made to treat position before Point degreasing.In some embodiments, the operation for cleaning treatment site is included in the forward direction skin to be treated of application composition Apply the 2- propyl alcohol of at least 70%w/w.The operation for making treatment site degreasing may include that alcohol is applied on skin, such as pass through wiping Apply, massage, placing, cleaning, denuding, wiping, swabbing or making in another way alcohol and skin contact.

In some embodiments, the method for the treatment of wart or wart related conditions further includes the treatment site debridement for subject The step of.In some embodiments, debridement operation may include it is mechanical, chemically or physically abrasion, ablation, thinning, strike off, break Bad, removal, excision or upset in another way skin to be treated or lesion surface (comprising reduce lesion thickness, And/or reduce the volume of lesion).In some embodiments, the step of debridement is applying this paper embodiment to treatment site Composition before, after, and/or while.

In some embodiments, alcohol can selected from primary alconol, secondary alcohol, the tertiary alcohol, or combinations thereof.Alcohol can be selected from methanol, second Alcohol, butanol, 1- propyl alcohol, amylalcohol, hexanol, octanol, nonyl alcohol, decyl alcohol, 2- butanol, 2- propyl alcohol, 2- amylalcohol, 2- hexanol, benzylalcohol, its is different Structure body, or combinations thereof.In some embodiments, the operation for making skin degreasing may include applying degreasing agent known to another kind It is added on skin and (such as ethyl acetate, butyl acetate is applied on skin), such as by rubbing, massaging, placement, clean, mill It loses, wipe, swabbing or contacting skin with agent in another way.In some embodiments, the operation of cleaning skin includes Apply antiseptic solution to skin to be treated or cutaneous lesions.In some embodiments, antibacterial agent be povidone, iodine, chlorine oneself Fixed, detergent, soap etc..

Some embodiments are related to treating the method for wart, and the method includes implementing herein to subject in need application The composition of scheme.In some embodiments, wart can be selected from wart, verruca vulgaris, recurrent wart, duration wart, verruca filiformis, life It grows device wart, external genital organs wart, periungual wart, subungual wart, plantar wart, mosaic warts, intractable wart, just control wart, palmoplantar verruca, verruca plana, wart Shape epidermodysplasia correlation wart, anogenital wart, condyloma acuminatum, cervical atypical hyperplasia or tumor-like lesion are (for example, uterine neck Intraepithelial neoplasia (CIN)), or combinations thereof.In some embodiments, composition includes the up to about peroxide of 60%w/w Change hydrogen.In some embodiments, composition includes the up to about hydrogen peroxide of 50%w/w.In some embodiments, it combines Object includes the up to about hydrogen peroxide of 45%w/w.In some embodiments, composition includes being greater than 40%w/w to about 60% The hydrogen peroxide of w/w.In some embodiments, composition includes the hydrogen peroxide of about 45%w/w.In some embodiments In, composition includes the pure and mild up to about hydrogen peroxide of 50%w/w.In some embodiments, composition include it is pure and mild up to The hydrogen peroxide of about 60%w/w.In some embodiments, composition includes the pure and mild mistake greater than 40%w/w to about 60%w/w Hydrogen oxide.In some embodiments, alcohol is 2- propyl alcohol.In some embodiments, alcohol is greater than 0%w/w to about 5%w/w 2- propyl alcohol.In some embodiments, composition include about 25%w/w hydrogen peroxide and be greater than 0%w/w to about 5%w/w 2- propyl alcohol.In some embodiments, composition include about 32.5%w/w hydrogen peroxide and be greater than 0%w/w to about 5% The 2- propyl alcohol of w/w.In some embodiments, composition includes being greater than the hydrogen peroxide of 40%w/w and being greater than 0%w/w to about The 2- propyl alcohol of 5%w/w.In some embodiments, composition includes the hydrogen peroxide of about 41%w/w and is greater than 0%w/w to about The 2- propyl alcohol of 5%w/w.In some embodiments, composition includes the hydrogen peroxide of about 42%w/w and is greater than 0%w/w to about The 2- propyl alcohol of 5%w/w.In some embodiments, composition includes the hydrogen peroxide of about 43%w/w and is greater than 0%w/w to about The 2- propyl alcohol of 5%w/w.In some embodiments, composition includes the hydrogen peroxide of about 44%w/w and is greater than 0%w/w to about The 2- propyl alcohol of 5%w/w.In some embodiments, composition includes the hydrogen peroxide of about 45%w/w and is greater than 0%w/w to about The 2- propyl alcohol of 5%w/w.In some embodiments, composition includes the hydrogen peroxide of about 46%w/w and is greater than 0%w/w to about The 2- propyl alcohol of 5%w/w.In some embodiments, composition includes the hydrogen peroxide of about 47%w/w and is greater than 0%w/w to about The 2- propyl alcohol of 5%w/w.In some embodiments, composition includes the hydrogen peroxide of about 48%w/w and is greater than 0%w/w to about The 2- propyl alcohol of 5%w/w.In some embodiments, composition includes the hydrogen peroxide of about 49%w/w and is greater than 0%w/w to about The 2- propyl alcohol of 5%w/w.In some embodiments, composition includes the up to about hydrogen peroxide of 60%w/w and 2- propyl alcohol.

In some embodiments, any one for the treatment of method described herein treatment wart can be used.It is some Embodiment is related to improving the method for the appearance of wart, and the method includes applying this paper embodiment to subject in need Composition.Some embodiments are related to mitigating the side of (for example, reduce, dimensionally reduce, and/or reduce in height) wart Method, the method includes the composition of this paper embodiment is applied to subject in need.In some embodiments, wart is Just control.In some embodiments, the treatment of any one for the treatment of method described herein can be used and just control wart.One A little embodiments are related to improving the method for the appearance for just controlling wart, and the method includes implementing herein to subject in need application The composition of scheme.Some embodiments be related to improve just control wart appearance method, the method includes to it is in need by Examination person applies the composition of this paper embodiment.Some embodiments, which are related to mitigating, just controls wart (for example, reducing, dimensionally subtracting It is small, and/or in height reduce) just control wart method, the method includes applying this paper embodiment party to subject in need The composition of case.In some embodiments, wart is not just to control wart either intractable wart.Intractable wart may include to other Therapy it is resistant or made other therapies fail or to other therapy parts response wart, wart difficult to treat or hardly possible With treatment or it is known to treatment with compared with low-response or with the wart in the anatomical position compared with high relapse rate.In some embodiments In, intractable wart may include plantar wart, periungual wart, subungual wart etc..In some embodiments, intractable wart can be located at any Body surface.In some embodiments, any one for the treatment of method described herein treatment intractable can be used Wart.Some embodiments are related to improving the method for the appearance of intractable wart, and the method includes applying to subject in need The composition of this paper embodiment.Some embodiments be related to improve intractable wart appearance method, the method includes to Subject in need applies the composition of this paper embodiment.Some embodiments are related to mitigating (for example, reducing, in size Upper reduction, and/or reduce in height) method of intractable wart, the method includes applying herein to subject in need The composition of embodiment.In some embodiments, subject realizes improvement or the portion of the patient's condition after being treated with composition It distinguishes and removes.In some embodiments, subject realizes the fully erased of wart after being treated with composition.In some embodiment party In case, subject reaches removing or slight doctor's wart assessment score after being treated with composition.In some embodiments, Subject realizes the reduction of at least one ordinal number in terms of doctor's wart assesses score after being treated with composition.In some implementations In scheme, subject realizes the reduction of at least two ordinal numbers in terms of doctor's wart assesses score after being treated with composition.? In some embodiments, subject realizes at least three ordinal numbers in terms of doctor's wart assesses score after being treated with composition Reduction.

Some embodiments are related to treating the method for the lesion of human papilloma virus induction, and the method includes in need Subject apply the composition of this paper embodiment.Some embodiments are related to the method for treating the lesion of poxvirus induction, The method includes the composition of this paper embodiment is applied to subject in need.Some embodiments are related to treatment and infect The method of property molluscum, the method includes the composition of this paper embodiment is applied to subject in need.In some implementations In scheme, subject realizes that the improvement of the patient's condition or part are removed after being treated with composition.In some embodiments, tested Person realizes the fully erased of the patient's condition after being treated with composition.In some embodiments, the method for molluscum contagiosum is treated Composition including applying from this paper embodiment to subject in need, wherein the amount of hydrogen peroxide is about 23%w/w to about 70%w/w.

Some embodiments of this paper are related to treating the method for skin conditions, and the method includes (i) local applications first The composition of this paper embodiment of dosage；And the composition of one or more subsequent doses of (ii) local application.One In a little embodiments, the application of the first dosage and one or more subsequent doses includes an application phase.In some embodiment party In case, subsequent dose is administered immediately after the application of the first dosage.In some embodiments, subsequent dose is at first dose It is administered at least about 0.5 minute after amount.In some embodiments, subsequent dose at least about 1 minute after the first dosage, At least about 1.5 minutes, at least about 2 minutes, at least about 5 minutes, at least about 10 minutes, at least about 15 minutes, at least about 20 minutes, It is administered at least about 25 minutes, at least about 30 minutes or at least 1 hour.In some embodiments, it is each apply it is interim can With there are after a subsequent dose, two subsequent doses, three subsequent doses, four subsequent doses, five subsequent doses, six Continuous dosage, seven subsequent doses, eight subsequent doses, nine subsequent doses or ten subsequent doses.Each subsequent subsequent dose Amount can be administered immediately after the application of preceding dose, at least about 1 minute, at least about 1.5 minutes after preceding dose, At least about 2 minutes, at least about 5 minutes, at least about 10 minutes, at least about 15 minutes, at least about 20 minutes, at least about 25 minutes, It is administered at least about 30 minutes or at least 1 hour.

In some embodiments, topical compositions can be administered with effective dose.In some embodiments, have This paper embodiment that effect dosage can be from about 0.0025 milliliter to about 3 milliliter composition (comprising about 0.0025 milliliter, about 0.01 milliliter, about 0.025 milliliter, about 0.04 milliliter, about 0.05 milliliter, about 0.075 milliliter, about 0.1 milliliter, about 0.12 milliliter, About 0.15 milliliter, about 0.16 milliliter, about 0.5 milliliter, about 1 milliliter, about 1.5 milliliters, about 2 milliliters, about 2.5 milliliters, about 3 milliliters, 4 Milliliter, 5 milliliters, 10 milliliters, 12 milliliters, a combination thereof or any amount to lesion with clinical effectiveness).In some embodiments In, effective dose is directly proportional to the size of lesion.In some embodiments, the effective dose of composition is less than every place's lesion about 0.12 milliliter.In some embodiments, effective dose can be about the composition of 0.2 milliliter of this paper embodiment.One In a little embodiments, effective dose can be the composition of this paper embodiment from about 0.01 milliliter to about 3 milliliter.Some In embodiment, effective dose can be the composition of this paper embodiment from about 0.01 milliliter to about 2 milliliter.In some realities It applies in scheme, effective dose can be the composition of this paper embodiment from about 0.01 milliliter to about 1 milliliter.In some implementations In scheme, effective dose can be the composition of this paper embodiment from about 0.01 milliliter to about 0.5 milliliter.In some implementations In scheme, effective dose can be the composition of this paper embodiment from about 0.01 milliliter to about 0.4 milliliter.In some implementations In scheme, effective dose can be the composition of this paper embodiment from about 0.01 milliliter to about 0.3 milliliter.In some implementations In scheme, effective dose can be the composition of this paper embodiment from about 0.01 milliliter to about 0.2 milliliter.In some implementations In scheme, effective dose can be the composition of this paper embodiment from about 0.02 milliliter to about 3 milliliter.In some embodiment party In case, effective dose can be the composition of this paper embodiment from about 0.02 milliliter to about 2 milliliter.In some embodiments In, effective dose can be the composition of this paper embodiment from about 0.02 milliliter to about 1 milliliter.In some embodiments In, effective dose can be the composition of this paper embodiment from about 0.02 milliliter to about 0.5 milliliter.In some embodiments In, effective dose can be the composition of this paper embodiment from about 0.02 milliliter to about 0.4 milliliter.In some embodiments In, effective dose can be the composition of this paper embodiment from about 0.02 milliliter to about 0.3 milliliter.In some embodiments In, effective dose can be the composition of this paper embodiment from about 0.02 milliliter to about 0.2 milliliter.

In some embodiments, the first dosage of local application and subsequent dose include massaging composition into skin, Each dosage massage at least about 5 seconds, at least about 10 seconds, at least about 15 seconds, at least about 20 seconds, at least about 25 seconds, at least about 30 seconds, At least about 35 seconds, at least about 40 seconds, at least about 45 seconds, at least about 50 seconds, at least about 55 seconds, at least about 1 minute, at least about 2 points Clock, at least about 3 minutes, at least about 4 minutes or at least about 5 minutes, at least about 10 minutes, at least about 15 minutes, at least about 20 points Clock, at least about 25 minutes or at least about 30 minutes.In some embodiments, composition is solution.In some embodiments In, composition is gel.In some embodiments, massage comprising rub into, massage, kneading, pressing or in another way " manipulation " composition enters skin.In some embodiments, apply composition with applicator and massage into skin.One In a little embodiments, apply composition within each application phase and massage at least 1 time, at least 2 times, at least 3 times, at least 4 times, In at least 5 times, at least 6 times, at least 7 times, at least 8 times, at least 9 times or at least 10 times entrance skins.In some embodiments In, apply composition the application phase can once a day, twice daily, once a week, twice a week, three-times-weekly, Mei Geyi It is primary, monthly, the every two moon is primary, every three months is primary, every six months it is primary or instruct quilt by packaging or doctor It repeats, to realize desired clinical effectiveness.

In some embodiments, composition is applied by healthcare provider.In some embodiments, composition exists It is administered under health care environment.In some embodiments, composition is by self application of subject in need.In some realities It applies in scheme, composition is applied by the care-giver of subject.As it is used herein, healthcare provider may include doctor Life, nurse, physician extenders, operation nurse, medical assistant or any professional people in the work of doctor's office, hospital or clinic Member.As it is used herein, health care environment refers to doctor's office, hospital, ambulatory care setting or clinic.Subject's Care-giver may include parent, nurse, friend, kinsfolk, medical professional or assist to apply to subject in need Anyone of composition.

In some embodiments, method further includes local from healthcare provider to subject after initial treatment Apply the second chamber as described in embodiments above including hydrogen peroxide and alcohol.In some embodiments, Two compositions are household compositions.In some embodiments, second chamber can be used as non-prescribed medicine acquisition.In some implementations In scheme, second chamber can be obtained by prescription.In some embodiments, second chamber may include that concentration is low In the hydrogen peroxide for the initial treatment applied to subject.In some embodiments, second chamber may include concentration with The identical hydrogen peroxide of initial treatment applied to subject.In some embodiments, second chamber includes up to about The hydrogen peroxide and alcohol of 60%w/w.In some embodiments, second chamber includes the hydrogen peroxide and alcohol of about 45%w/w. In some embodiments, second chamber includes the alcohol of the hydrogen peroxide and 5%w/w greater than 40%w/w.In some embodiment party In case, second chamber includes being greater than 40%w/w to the hydrogen peroxide of about 60%w/w and the alcohol of 5%w/w.In some embodiment party In case, second chamber includes the hydrogen peroxide of about 45%w/w and the alcohol of 5%w/w.In some embodiments, the second combination Object includes the hydrogen peroxide of about 50%w/w and the alcohol of 5%w/w.In some embodiments, second chamber includes about 54%w/ The hydrogen peroxide of w and the alcohol of 5%w/w.In some embodiments, second chamber include about 55%w/w hydrogen peroxide and The alcohol of 5%w/w.In some embodiments, second chamber includes the hydrogen peroxide of about 59%w/w and the alcohol of 5%w/w.? In some embodiments, second chamber includes the hydrogen peroxide of about 40%w/w and the alcohol of 5%w/w.In some embodiments In, second chamber includes the hydrogen peroxide of about 35%w/w and the alcohol of 5%w/w.In some embodiments, second chamber The alcohol of hydrogen peroxide and 5%w/w including about 32.5%w/w.In some embodiments, second chamber includes about 25%w/ The hydrogen peroxide of w and the alcohol of 5%w/w.In some embodiments, the amount of the hydrogen peroxide in second chamber can be about 0.5%w/w, about 5%w/w, about 10%w/w, about 15%w/w, about 20%w/w, about 23.5%w/w, about 25%w/w, about 30% W/w, about 32.5%w/w, about 35%w/w, about 40%w/w, about 41%w/w, about 42%w/w, about 43%w/w, about 44%w/w, About 45%w/w, about 46%w/w, about 47%w/w, about 48%w/w, about 49%w/w, about 50%w/w, about 51%w/w, about 52% W/w, about 53%w/w, about 54%w/w, about 55%w/w, about 56%w/w, about 57%w/w, about 58%w/w, about 59%w/w, about The range of 60%w/w, about 65%w/w, about 70%w/w or any two in these values.In some embodiments, alcohol is 2- propyl alcohol.In some embodiments, second chamber can be by self application of subject.It in some embodiments, can be with At least about 1 day, at least about 2 days, at least about 3 days, at least about 1 week, at least about 2 weeks, at least about 3 weeks after initial treatment, extremely Lack about 4 weeks, at least about 5 weeks, at least about 6 weeks, at least about 7 weeks or to maintain clinical effectiveness or up to lesion is needed for removing Interval second chamber is applied by health care professional.In some embodiments, second chamber can once a day, Twice daily, once a week, twice a week, every other day, monthly, the every two moon is primary, every three months is primary, six every The moon is primary or is administered by packaging or doctor's guidance, to realize desired clinical effectiveness.

Some embodiments of this paper are related to the method that skin conditions are treated in subject, and the method includes to tested Person's local application includes the household compositions of hydrogen peroxide and alcohol as described above.In some embodiments, Combined household Object can be used as non-prescribed medicine acquisition.In some embodiments, household compositions can be obtained by prescription.In some implementations In scheme, household compositions include the up to about hydrogen peroxide of 60%w/w and alcohol.In some embodiments, household compositions Hydrogen peroxide and alcohol including about 60%w/w.In some embodiments, household compositions include the peroxidating of about 50%w/w Hydrogen and alcohol.In some embodiments, household compositions include the hydrogen peroxide and alcohol of about 55%w/w.In some embodiments In, household compositions include the hydrogen peroxide of about 45%w/w and the alcohol of 5%w/w.In some embodiments, household compositions The alcohol of hydrogen peroxide and 5%w/w including about 40%w/w.In some embodiments, household compositions include about 35%w/w Hydrogen peroxide and 5%w/w alcohol.In some embodiments, household compositions include about 32.5%w/w hydrogen peroxide and The alcohol of 5%w/w.In some embodiments, household compositions include the hydrogen peroxide of about 25%w/w and the alcohol of 5%w/w.? In some embodiments, alcohol is 2- propyl alcohol.Such household compositions can be applied after health care professional going to a doctor. In some embodiments, household compositions can be applied after initial treatment by health-care professional.In some implementations In scheme, household compositions may include the hydrogen peroxide that concentration is lower than the initial treatment applied to subject.In some implementations In scheme, household compositions may include concentration hydrogen peroxide identical with the initial treatment applied to subject.Combined household Object can be by self application of subject.In some embodiments, can after initial treatment at least about 1 day, at least about 2 It, family was applied by health care professional at least about 3 days, at least about 1 week, at least about 2 weeks, at least about 3 weeks, at least about 4 weeks Use composition.In some embodiments, household compositions can once a day, twice daily, once a week, twice a week, Every other day, monthly, the every two moon is primary, every three months is primary, every six months it is primary or instruct quilt by packaging or doctor Application, to realize clinically desirable result.In some embodiments, household compositions can be administered one day, one week, two Week, three weeks, surrounding, five weeks, six weeks, seven weeks, eight weeks, nine weeks, ten weeks, 11 weeks, 12 weeks periods or press and pack or cure Any duration of teacher's guidance, to realize clinically desirable result.

Embodiments herein also cover the hydrogen peroxide composition for applying this paper embodiment device (referring to, For example, Figure 12-16 and related description).In some embodiments, any local applicator known in the art can be used to apply With the composition for as described in this paper embodiment including hydrogen peroxide and alcohol.In some embodiments, it can be used Sponge, swab, foam head stick (foam tipped stick), cotton balls, brush, Woven fabric or supatex fabric, roll of gauze, The applications such as gauze, pen, gloves include the composition of hydrogen peroxide and alcohol as described in this paper embodiment.In some implementations In scheme, applicator can be via flocking, absorbability, and/or sufficiently tight to apply the distribution of stressed tip herein to lesion The composition of embodiment.In some embodiments, applicator is sintered polymer tip applicator.In some embodiments In, it is applicator resisting high-concentration peroxide solutions, compatible with high concentration peroxide solutions or molten to high concentration peroxide Liquid is inert.In some embodiments, applicator can distribute solution with controlled rate, to help to limit activating agent The normal skin of surrounding is not injured to interested lesion and.In some embodiments, can be used has in compartment The device of hydrogenperoxide steam generator applies solution, and solution is assigned to applicator tip when needed or passes through applicator by described device Solution is distributed at tip.In some embodiments, applicator may include being designed with before composition is applied, later or apply Used time denudes the material of cutaneous lesions or treatment site.In some embodiments, applicator is hind foot applicator (doe footed applicator).In some embodiments, applicator is flocking hind foot applicator.In some embodiments In, flocking hind foot applicator is made of HDPE (high density polyethylene (HDPE)), nylon and adhesive.In some embodiments, molten Liquid once a day, twice daily, once a week, twice a week, three-times-weekly, it is every other day primary, monthly, the every two moon Once, every three months is primary or is applied by packaging or doctor or supplier guidance, to realize desired clinical effectiveness.

In some embodiments, the method for treating skin conditions includes applying the composition of this paper embodiment.One In a little embodiments, the operation for applying the composition of this paper embodiment includes the nib contacts for making treatment site and applicator, Wherein applicator includes the suitable container that composition is disposed therein.In some embodiments, this paper embodiment party is applied The operation of the composition of case includes the nib contacts for making treatment site and applicator, and wherein applicator includes topical compositions The frangible ampoule that is disposed therein, is connected to the applicator main body that has frangible ampoule to be disposed therein with applicator body fluid Applicator hub, be arranged in applicator hub proximal end tip and the filter that is arranged between frangible ampoule and tip.One In a little embodiments, the operation for applying topical compositions includes that the extruding on applicator body exterior surface is applied to by changing Power controls the flow velocitys of the topical compositions for leaving tip.In some embodiments, the operation of topical compositions is applied Including contacting tip with the target lesions of skin conditions, topical compositions are assigned to target lesions by tip whereby On.In some embodiments, the operation for applying topical compositions further includes to being arranged on applicator body outer surface Pressure span applies pressure, ruptures frangible ampoule.In some embodiments, the operation for applying topical compositions includes making Frangible ampoule ruptures and passes through tip release topical compositions；And contact tip with the target lesions of skin conditions.

Some embodiments of this paper are related to the kit for treating skin conditions, and the kit includes container and makes With specification, the container includes the compartment with hydrogen peroxide, the compartment with 2- propyl alcohol.Some embodiments of this paper relate to And the kit for treating skin conditions, the kit include container and operation instructions, the container includes peroxidating Hydrogen and 2- propyl alcohol.Some embodiments are related to the kit for treating skin conditions, and the kit includes container and use Specification, the container include hydrogen peroxide and 2- propyl alcohol.In some embodiments, kit further includes applicator.One In a little embodiments, kit may include two or more applicators.For example, in some embodiments, it is super existing In the case where crossing a lesion to be treated (for example, in over the counter kit or in the kit by doctor's multiple applications) or If in the case that person's kit also includes the household preparations for the composition repeatedly applied, kit can contain there are many applying Add device.In some embodiments, kit may include with the breakaway glass ampoule with hydrogenperoxide steam generator and alcohol Applicator.In some embodiments, kit may include applying with the breakaway glass ampoule with hydrogenperoxide steam generator Add device, wherein applicator also includes the compartment with alcohol (such as (but not limited to) 2- propyl alcohol) in applicator main body.In some realities It applies in scheme, applicator can also include the compartment with gelling agent.In some embodiments, kit may include two Or more part use hydrogen peroxide preparation container.In some embodiments, two or more part hydrogen peroxide The container of preparation may include the hydrogen peroxide preparation of identical concentration of hydrogen peroxide.In some embodiments, two or more The container of a part hydrogen peroxide preparation may include the hydrogen peroxide preparation of different concentration of hydrogen peroxide.For example, some In embodiment, it includes the hydrogen peroxide for being greater than 40%w/w that kit, which may include for what is applied in an office by doctor, Taken home with the container of the 2- propyl alcohol of 5%w/w and for patient with apply then to target site various concentration (for example, compared with Dilute concentration) hydrogen peroxide other containers.In some embodiments, kit may include two or more with more The disposable container of the part of a applicator hydrogen peroxide preparation.In some embodiments, kit may include container, The container has the multi-dose container of the part hydrogen peroxide preparation with multiple applicators.Skin conditions can be virus The skin growth or hyperplasia of induction or non-viral induction.In some embodiments, skin conditions can be selected from human papilloma The lesion of virus induction, for example, wart, verruca vulgaris, palmoplantar verruca, verruca plana, recurrent wart, verruca filiformis, external genital organs wart, genitals Wart, intractable wart just control wart, epidermodysplasia verruciformis correlation wart, anogenital wart, condyloma acuminatum, the increasing of uterine neck atypia Raw or tumor-like lesion (for example, cervical intraepithelial neoplasia (CIN) (CIN))；Poxvirus induction lesion (for example, molluscum contagiosum or Oof), or combinations thereof lesion.In some embodiments, applicator can selected from sponge, swab, foam head stick, cotton balls, Brush, Woven fabric or supatex fabric, roll of gauze, gauze, pen etc..In some embodiments, applicator is flocking, absorbs Property, and/or it is sufficiently tight with to lesion apply pressure.In some embodiments, applicator is that sintered polymer tip is applied Add device.In some embodiments, applicator resisting high-concentration peroxide solutions, it is compatible with high concentration peroxide solutions or It is inert to high concentration peroxide solutions.In some embodiments, applicator can distribute solution with controlled rate, with Just the normal skin that activating agent is restricted to interested lesion and does not injure surrounding is helped.In some embodiments, may be used So that the device being used in compartment with hydrogenperoxide steam generator applies solution, solution is assigned to application when needed by described device Solution is distributed by applicator tip in device tip.In some embodiments, applicator may include being designed to combine Denuded before object application or when apply cutaneous lesions or treatment site or for cutaneous lesions or treatment site debridement material or Feature.In some embodiments, applicator has material or feature, mechanically or physically to enhance hydrogen peroxide to lesion Interior infiltration or the therapeutic efficiency for enhancing composition in another way.In some embodiments, the material of applicator or Feature is designed to polish before applying topical compositions the treatment site of subject, file, strike off, denude or clearly Wound.

In some embodiments, applicator is hind foot applicator.In some embodiments, applicator is that flocking is female Deer foot applicator.In some embodiments, flocking hind foot applicator is by HDPE (high density polyethylene (HDPE)), LDPE (low-density Polyethylene), nylon, adhesive, or any combination thereof composition.In some embodiments, container can selected from bottle, ampoule, Tank, bottle, pencil, syringe or any other container for storing liquid.In some embodiments, compartment can be selected from Bottle, pipe, ampoule, tank, bottle, pencil, syringe or any other container for storing liquid.In some embodiments, Container can be glass, Pyrex, I type Pyrex, coloured glass or other be protected from light glass, amber glass, amber I Type Pyrex, HDPE,Silicone, ABS (acronitrile-butadiene-styrene) or other compatible polymers or material Material.In some embodiments, kit can wrap the vial or glass being disposed therein containing hydrogenperoxide steam generator and alcohol Glass bottle.In some embodiments, vial or vial may include amber glass bottle or amber glass bottle.? In some embodiments, kit may include at least partly being formed by HDPE of having hydrogenperoxide steam generator and alcohol to be disposed therein Bottle or bottle.In some embodiments, container can be by with peroxide there is the material of hypoergia to be formed.Some In embodiment, compartment may include the material for having hypoergia with peroxide.In some embodiments, hydrogen peroxide It is stabilized hydrogen peroxide.In some embodiments, the hydrogen peroxide in one or more containers of kit can be with For the amount of any embodiment described herein, the amount includes, for example, being greater than 40%w/w, about 45%w/w, about 50%w/ W, about 54%w/w, about 55%w/w, about 59%w/w, about 60%w/w.In some embodiments, alcohol (such as (but not limited to) 2- Propyl alcohol) amount be less than about 25%w/w (including, for example, about 5%w/w or about 2.5%w/w).In some embodiments, reagent Box can be used for healthcare provider.In some embodiments, kit can be used for subject in need.? In some embodiments, kit can only be obtained through prescription.In some embodiments, kit can be used as non-prescribed medicine and obtain , it is used for subject in need.

Some embodiments of this paper are related to the device of the composition for applying this paper embodiment.In some embodiment party In case, device may include applicator, and the applicator is configured to the composition of this paper embodiment securely and effectively It is delivered to the target skin of patient.Some embodiments of this paper include applicator, and the applicator is configured to store and divide With topical compositions, the topical compositions include the agent selected from escharotic, unstable dose or combinations thereof, the applicator Include topical compositions be disposed therein frangible ampoule, there is frangible ampoule to be disposed therein applicator main body, with apply Add device body fluid be connected to applicator hub, be arranged in applicator hub proximal end tip and be arranged in frangible ampoule and point Filter between end.In some embodiments, topical compositions include the peroxide from about 40%w/w to about 60%w/w Change hydrogen and the 2- propyl alcohol greater than 0%w/w to about 5%w/w.In some embodiments, agent includes the peroxidating from about 40%w/w Hydrogen to about 60%w/w hydrogen peroxide.In some embodiments, frangible ampoule also includes greater than 0%w/w to about 5%w/w 2- propyl alcohol.In some embodiments, applicator main body further includes the supplementary element for the topical compositions being disposed therein, and is borrowed This before applying topical compositions, agent in response to frangible ampoule rupture from frangible ampoule release and with applicator main body In supplementary element mixing.In some embodiments, topical compositions are ruptured from frangible ampoule in response to frangible ampoule It discharges and flows through applicator main body, filter and applicator is left by tip.In some embodiments, apply Device also includes the pressure span being arranged on the outer surface of applicator main body, to indicate that a part of applicator main body applies pressure Rupture frangible ampoule.

Some embodiments are related to the applicator for being configured to store and distribute topical compositions, the topical composition Object includes the 2- propyl alcohol from about 25%w/w to the hydrogen peroxide of about 60%w/w and greater than 0%w/w to about 5%w/w, the application Device include topical compositions be disposed therein frangible ampoule, there is frangible ampoule to be disposed therein applicator main body, with Applicator body fluid connection applicator hub, be arranged in applicator hub proximal end tip and be arranged in frangible ampoule with Filter between tip.In some embodiments, frangible ampoule by glass, plastics, Pyrex, 1 type Pyrex and The formation of at least one of coloured glass.In some embodiments, applicator main body is by polypropylene, high density polyethylene (HDPE), low Density polyethylene, polyvinyl chloride, polyethylene, or combinations thereof formed.In some embodiments, filter is configured to prevent brokenly The fragment for the frangible ampoule split passes through and topical compositions is allowed to flow through.In some embodiments, filter by Polypropylene, high density polyethylene (HDPE), low density polyethylene (LDPE), polyethylene, polystyrene, ceramic material, foamed material, sand, diatomite It is formed at least one of paper fiber.

Some embodiments are related to treating the method for skin conditions, include up to the method includes using applicator application The topical compositions of the hydrogen peroxide of about 60%w/w and the 2- propyl alcohol greater than 0%w/w to about 5%w/w, the applicator packet Include the frangible ampoule that topical compositions are disposed therein, the applicator main body and application that there is frangible ampoule to be disposed therein Device body fluid connection applicator hub, be arranged in applicator hub proximal end tip and be arranged in frangible ampoule and tip Between filter.In some embodiments, the operation for applying topical compositions includes to the outer surface of applicator main body Apply extruding force to distribute composition.In some embodiments, the operation for applying topical compositions includes making tip and skin The target lesions of the skin patient's condition contact, and topical compositions are assigned to target lesions by tip whereby.In some embodiments, The operation of application topical compositions further includes applying pressure to the pressure span being arranged on applicator body outer surface, is made easily Broken ampoule fractures.In some embodiments, the operation for applying topical compositions includes rupturing frangible ampoule and passing through Tip release topical compositions；And contact tip with the target lesions of skin conditions.

In some embodiments, applicator, which may include, is arranged in applicator master intracorporal to be configured to storage real herein Apply the frangible ampoule of the composition of scheme.In some embodiments, ampoule can be by glass or other similar friable material (such as Pyrex) are formed.In some embodiments, applicator main body can be formed by various flexible materials, the flexibility material Material is including (but not limited to) high density polyethylene (HDPE) (HDPE), low density polyethylene (LDPE) (LDPE) or its various combination or admixture.? It, can be by applying the hand for being enough that ampoule is made to split on the direction towards ampoule in applicator main body in some embodiments Dynamic pressure (for example, " extruding "), discharges the composition of this paper embodiment from ampoule.In some embodiments, from peace The composition of this paper embodiment discharged in small jar can flow through filter, and the filter is configured to filtering from broken The glass fragment of broken ampoule, while the composition of this paper embodiment being allowed to flow through the filter.In some implementations In scheme, at least one portion of applicator may include hydrophobic material, such as filter and/or tip.In some embodiment party In case, hydrophobic material by polyester or copolyester polymer, acrylic compounds, modified acrylic acid (for example, modacrylic), Polypropylene, polyethylene, or combinations thereof or mixture composition.The non-limiting example of hydrophobic material can also include comprising silicon Alkane, alkyl silane, fluoro alkyl-silane, silicone, a combination thereof and its derivative material, be coated with silane, alkyl silane, fluothane Base silane, silicone, a combination thereof and its derivative material, and/or through silane, alkyl silane, fluoro alkyl-silane, silicone, its group Conjunction and its derivative modified material.In some embodiments, the hydrophobic parts of applicator can work with prevent, The composition for reducing, limit, preventing and/or basically preventing this paper embodiment discharged from ampoule, which flows through, to be applied Add the multiple portions of device and/or leaves the tip of applicator.In some embodiments, the composition of this paper embodiment can be with It flows through filter and leaves applicator via applicator tip to apply on the skin of the patient.In some embodiments In, tip may include the flocked portion formed by the filament (such as nylon) of various chemical compatibilities and non-reactive material.

Figure 11 describes the illustrative applicator configured according to first embodiment.As shown in Figure 11, applicator 1200 can To include applicator main body 1205.In some embodiments, applicator pipe 1205 can be closed in its distal end by end cap 1215. In some embodiments, applicator main body 1205 and/or end cap 1215 can by various flexible materials (including (but not limited to) Flexible polymer material) it is formed.The non-limiting example of flexible polymer material may include polypropylene (PP), high-density polyethylene Alkene (HDPE) or low density polyethylene (LDPE) (LDPE), polyvinyl chloride (PVC), polyethylene (PE), its derivative and any combination thereof. In some embodiments, applicator main body 1205 can have shape approximately longitudinally.In some embodiments, applicator Main body 1205 can have the shape of generally cylindrical body.According to some embodiments, applicator main body 1205 can have various Length, the length include about 80 millimeters, about 90 millimeters, about 98 millimeters, about 99 millimeters, about 100 millimeters, about 110 millimeters, about 120 millimeters, about 130 millimeters, about 140 millimeters, about 150 millimeters, about 80 millimeters to about 100 millimeters, about 80 millimeters to about 150 millis In rice, about 90 millimeters to about 100 millimeters, about 100 millimeters to about 120 millimeters, about 100 millimeters to about 150 millimeters and these values Any value or range (including endpoint) between any.According to some embodiments, applicator main body 1205 can have various External measurement, the scale include about 5 millimeters, about 7 millimeters, about 9 millimeters, about 10 millimeters, about 12 millimeters, about 15 millimeters, about 18 Millimeter, about 20 millimeters, about 5 millimeters to about 7 millimeters, about 5 millimeters to about 10 millimeters, about 7 millimeters to about 10 millimeters, about 9 millimeters extremely In about 15 millimeters, about 10 millimeters to about 15 millimeters, about 5 millimeters to about 20 millimeters, about 10 millimeters to about 20 millimeters and these values Any value or range (including endpoint) between any.

In some embodiments, the ampoule 1210 for being configured as the composition of storage this paper embodiment can be arranged In the chamber formed in applicator main body 1205.In some embodiments, ampoule 1210 can be frangible, for example, by matching It sets to be crushed, fragmentation, rupture, broken or in another way split in response to applying enough pressure to it.For example, Enough pressure can be applied manually, e.g., by manpower (for example, by squeezing or pressing) in court in applicator main body 1205 The region applied force of the applicator main body positioned on the direction of ampoule 1210 in ampoule.In this way, to applicator master The power that body 1205 applies can be transferred to ampoule 1210 and ampoule can split in response to applying enough power to it.One In a little embodiments, ampoule 1210 (can include glass, plastics, polymer material, Pyrex, I type by various friable materials Pyrex, coloured glass and any combination thereof) it is formed.In some embodiments, ampoule 1210 may include one or more Multiple atenuator regions, to facilitate the rupture of ampoule 1210.In some embodiments, the composition of this paper embodiment can be severe Property and/or can be with the material or environment reaction of applicator 1200.In some embodiments, the combination of this paper embodiment Object can be degraded or contaminated object and/or the contact with environment influence in another way.Therefore, use is one or more The composition that a ampoule 1210 stores this paper embodiment can protect the group of 1200 material of applicator and/or this paper embodiment Object is closed from degradation, until it is discharged from ampoule.By using ampoule 1210, inter alia, applicator 1200 can be with Allow to store the composition and other components of this paper embodiment safe and stablely, until needing to deliver.

The composition for this paper embodiment being stored in ampoule 1210 can apply in response to being crushed for ampoule 1210 Release in device main body 1205.Ampoule 1210 can be configured to accommodate the composition of this paper embodiment of various volumes, described Volume includes about 0.1 milliliter, about 0.2 milliliter, about 0.5 milliliter, about 1 milliliter, about 1.5 milliliters, about 2 milliliters, about 2.4 milliliters, about 3 Milliliter, about 3.2 milliliters, about 4 milliliters, about 5 milliliters, about 10 milliliters, about 20 milliliters, about 30 milliliters, about 50 milliliters, about 100 milliliters, About 500 milliliters, about 0.1 milliliter to about 3 milliliters, about 0.1 milliliter to about 4 milliliters, about 0.1 milliliter to about 5 milliliters, about 0.1 milliliter To about 10 milliliters, about 0.1 milliliter to about 100 milliliters, about 0.1 milliliter to about 500 milliliters, about 1 milliliter to about 3 milliliters, about 1 milliliter To about 4 milliliters, about 1 milliliter to about 5 milliliters, about 1 milliliter to about 100 milliliters, about 1 milliliter to about 500 milliliters, about 2 milliliters to about 3 Milliliter, about 2 milliliters to about 4 milliliters, about 2 milliliters to about 5 milliliters, about 2 milliliters to about 10 milliliters, about 3 milliliters to about 4 milliliters, about 3 Milliliter to about 5 milliliters, about 3 milliliters to about 10 milliliters, about 3 milliliters to about 100 milliliters, about 4 milliliters to about 5 milliliters, about 4 milliliters extremely About 10 milliliters, about 4 milliliters to about 100 milliliters, about 5 milliliters to about 10 milliliters, about 5 milliliters to about 100 milliliters, about 100 milliliters extremely In about 500 milliliters and these values it is any between any value or range (including endpoint).In some embodiments, ampoule 1210 can be configured to accommodate the composition of this paper embodiment of effective dose.In some embodiments, ampoule 1210 It can be configured to accommodate the composition of this paper embodiment for the effective dose for being enough to treat single target lesion or skin area. In some embodiments, ampoule 1210 can be configured to accommodate the effective agent for being enough to treat multiple target lesions or skin area The composition of this paper embodiment of amount.In some embodiments, effective dose can be the milli from about 0.0025 milliliter to about 3 Rise this paper embodiment composition, comprising about 0.0025 milliliter, about 0.01 milliliter, about 0.025 milliliter, about 0.05 milliliter, About 0.075 milliliter, about 0.1 milliliter, about 0.15 milliliter, about 0.5 milliliter, about 1 milliliter, about 1.5 milliliters, about 2 millimeters, about 2.5 millis Liter, about 3 milliliters, a combination thereof or any amount to lesion with clinical effectiveness.In some embodiments, effective dose and disease The size of change is directly proportional.In some embodiments, the effective dose of composition is less than about 0.1 milliliter of every place's lesion.Some In embodiment, effective dose can be about the composition of 3 milliliters of this paper embodiment.In some embodiments, effectively Dosage can be the composition of this paper embodiment from about 2 milliliters to about 3 milliliter.In some embodiments, effective dose It can be the composition of this paper embodiment from about 2 milliliters to about 5 milliliter.

Although depicting only an ampoule 1210 in Figure 11, embodiment is not so limited, because of applicator 1200 may include multiple ampoules.For example, applicator 1200 may include the combination of this paper embodiment for multiple dosage Multiple ampoules 1210 of object.In another case, applicator 1200 may include the ampoule of multiple accommodating different components 1210.In some embodiments, applicator 1200 may include accommodating first chamber (for example, gelling agent, hydrogen peroxide) Compartment (not shown) and the one or more of second chambers of one or more accommodatings (for example, 2- propyl alcohol, this paper embodiment party The composition of case) ampoule 1210.For example, one or more walls applicator main body can be separated into it is one or more every Room part.In some embodiments, compartment or part thereof (for example, wall part that compartment is formed in applicator main body 1205) It can be crushed and applying enough power to compartment.In some embodiments, one or more first can be combined Object is set in applicator main body 1205, so that being set to one or more ampoules 1210 and/or one or more compartments Interior one or more of second chambers can in response to one or more of second chambers release and contact it is a kind of or More kinds of second chambers.The non-limiting example of first chamber can wrap alcohol-containing (for example, 2- propyl alcohol) or gelling agent, and The non-limiting example of second chamber may include causticity preparation (such as hydrogenperoxide steam generator).In some embodiments, respectively Kind composition (for example, one or more of first chambers and one or more of second chambers) can be before its application Or it mixes simultaneously.

In some embodiments, applicator hub 1225 can applicator 1200 proximal end and applicator main body 1205 It is in fluid communication.Applicator hub 1225 can be configured to the composition in response to this paper embodiment from the release of ampoule 1210 and Receive the composition of this paper embodiment flowed out from applicator main body 1205.In some embodiments, applicator hub 1225 At least part can be arranged in applicator main body 1205.In some embodiments, applicator hub 1225 can be consolidated Surely be attached to applicator main body 1205, such as by using adhesive, frictional fit, press-in cooperation, be threadedly engaged.In some realities It applies in scheme, the exterior section of applicator hub 1225 can be fixedly attached to the interior section of the proximal end of applicator main body 1205. In some embodiments, applicator hub 1225 can by frictional fit, adhesive, be threadedly engaged etc. and applicator main body 1205 form gas tight seal.In some embodiments, applicator hub 1225 can be by polymer material (comprising (unlimited In) PE, PP, HDPE and LDPE) formed.In some embodiments, protection cap 1235 can be configured to applicator hub 1225 are enclosed in the proximal end of applicator 1200.

In some embodiments, filter 1220 can be arranged in applicator 1200 between ampoule 1210 and applicator Between 1200 proximal end.In some embodiments, filter 1220 can be arranged in applicator hub 1225 towards ampoule In 1210 distal portions.Filter 1220 can be configured to filter out the fragment of broken ampoule 1210, while allow this The composition of literary embodiment flows through the filter.Filter 1220 can (including can be by ampoule by a variety of materials Any material that fragment is filtered out from the composition of this paper embodiment) it is formed.The non-limiting reality of 1220 material of filter Example may include various polymer materials (PE, PP, HDPE, LDPE, polystyrene (PS), carbon, foamed material, ceramics, sand, silicon Diatomaceous earth (DE), paper fiber and any combination thereof).In some embodiments, it can choose 1220 material of filter, to provide The composition of this paper embodiment passes through the specific flow velocity of filter.

In some embodiments, applicator 1200 may include the tip 1230 for being arranged in its proximal part.Some In embodiment, tip 1230 can be fixedly arranged in the centre bore of applicator hub 1225.Tip 1230 can be configured to The composition of this paper embodiment is applied on the skin of patient by convenience.In some embodiments, tip 1230 can be by Absorbent material or substantially absorbent material is formed.In some embodiments, it is poly- to may be configured to sintering for tip 1230 Close object tip.In some embodiments, tip 1230 may be configured to hind toe end.In some embodiments, sharp End 1230 may be configured to flocked tip end, for example, it (includes (but not limited to) by each that the flocked tip end, which may include flocked material, The suede that the filament of kind material is formed) and/or (can include (but not limited to) to be formed by the filament of a variety of materials by flocked material Suede) it is formed.In some embodiments, flocked tip end can be formed on tip 1230 by pasting flocked material.One In a little embodiments, tip 1230 can by do not reacted with the composition of this paper embodiment or in other aspects with implement herein The a variety of materials of the composition chemical compatibility of scheme are formed.In some embodiments, tip 1230 can be by various biofacies Capacitive material is formed.In some embodiments, tip 1230 can be formed by a variety of materials, and the material includes (but not limited to) Cellulose, nylon, artificial silk, polyester,Its fiber, its flocked material and any combination thereof.

In some embodiments, tip 1230 can be as frictional fit, being threadedly engaged, sliding into or locking by adhesive Tight fit, press-in cooperation etc. are fixedly arranged in applicator 1200 (such as in applicator hub 1225).In some embodiments, it applies Add device 1200 that can be configured to during each use or allow to replace tip 1230 every time after use.In some embodiment party In case, ampoule 1210 can be replaced in applicator 1200.For example, operator can remove end cap 1215, broken peace is removed The fragment of small jar 1210, and it is inserted into the new ampoule of the identical and/or different composition with this paper embodiment.With this Mode, applicator 1200 can be used for multiple times and/or for treating same patient multiple dermatosis condition (that is, individually lesion, Wart or other skin formations).In some embodiments, applicator 1200 can be disposable applicator.In some implementations In scheme, disposable applicator be directed at it is disposable after be dropped.

In some embodiments, the composition of this paper embodiment can be discharged and be flowed through from ampoule 1210 Applicator main body 1205 (including its any chamber), filter 1220, applicator hub 1225, and left and applied by tip 1230 Add device.In some embodiments, applicator main body 1205 and/or tip 1230 can be configured to allow operator's control severe Property preparation leaves the flowing of applicator 1200.In non-limiting example, this paper embodiment composition from ampoule After being discharged in 1210, operator can by being squeezed in applicator main body 1205, to generating enough pressure wherein To force the composition of this paper embodiment to leave application by the composition that tip 1230 flows out initiation this paper embodiment The flowing of device 1200.In some embodiments, operation of the pressing of tip 1230 on patient skin be can produce into capillary Effect, the capillarity are enough to make release and the group with this paper embodiment of nib contacts from ampoule 1210 Object is closed to flow through tip and leave applicator 1200.In some embodiments, operator can be by changing for squeezing The level of the side and/or the power by the pressing of tip 1230 on the skin of the patient of pressing applicator main body 1205 carrys out coutroi velocity. In some embodiments, applicator 1200, which may include, is configured so that the composition of this paper embodiment is distributed from applicator Actuator (not shown).

In some embodiments, at least one portion of applicator may include hydrophobic material, such as filter 1220 The tip 1230 and/or.In some embodiments, hydrophobic material is by polyester or copolyester polymer, acrylic compounds, modified third Olefin(e) acid class (for example, modacrylic), polypropylene, polyethylene, or combinations thereof or mixture composition.In some embodiments In, for example, filter may include the admixture of polypropylene and polyester or copolyester polymer.Hydrophobic material it is non-limiting Example can also include the material comprising silane, alkyl silane, fluoro alkyl-silane, silicone, a combination thereof and its derivative, coating Have a material of silane, alkyl silane, fluoro alkyl-silane, silicone, a combination thereof and its derivative, and/or through silane, alkyl silane, Fluoro alkyl-silane, silicone, a combination thereof and its derivative modified material.In some embodiments, can by coating or with Other mode mixes hydrophobic material wherein to assign and be used to form application according to some embodiments described herein Device and its partial material are with hydrophobicity.In some embodiments, the hydrophobic parts of applicator can work with prevent, The composition for reducing, preventing, and/or basically preventing this paper embodiment discharged from ampoule flows through applicator Multiple portions and/or leave the tip of applicator.

In some embodiments, applicator 1200 can be configured such that the implementation herein discharged from ampoule 1210 The composition of scheme applies pressure (as by squeezing or in another way to applicator main body to applicator in no operator 1205 applied forces) in the case where cannot passively from applicator 1200 distribute.In some embodiments, operator is acted The requirement of (that is, apply to applicator 1200 pressure) can by using according to the hydrophobic material of some embodiments come just Benefit.In some embodiments, can be configured such that can be in applicator main body 1205 from ampoule for applicator 1200 (for example, hanging down vertically, substantially when applicator is oriented in after the composition of this paper embodiment of the certain volume of 1210 releases When straight or vertical part position) form gap.In some embodiments, gap can play vacuum to prevent, drop Composition that is low, limiting, prevent, and/or basically prevent this paper embodiment discharged from ampoule 1210 leaves applicator 1200 flowing.In this way, the hydrophobic parts of applicator 1200 and/or the interior gap formed of applicator main body 1205 can To work, (to include at applicator after being discharged in frangible ampoule 1210 in the composition of this paper embodiment When helping to distribute position (such as vertical position or the substantially vertical position) of composition of this paper embodiment) it prevents Leakage of the composition of this paper embodiment from applicator.

Applicator 1200 can be configured to any one of storage, distribution and the composition for applying this paper embodiment A part for the treatment of method as any one of the patient's condition disclosed herein.For example, applicator 1200 can be configured to Storage, distribution and the topical compositions for applying the hydrogen peroxide including 2- propyl alcohol and up to about 60%w/w.In some embodiment party In case, topical compositions can be any composition described in this paper embodiment.

Although embodiment described in this paper is described with " comprising ", whole foregoing embodiments also include only The composition and method for being made of cited ingredient or step or being substantially made of cited ingredient and step, and not The optionally supplementary element or step of the basic and novel property of substantial effect composition or method.

The disclosure can be further understood by reference to following non-limiting examples and illustrates used method and material The embodiment of material.

Embodiment 1

With the 2- propyl alcohol of hydrogen peroxide (FMC/PeroxiChem " Super D ") and 5%w/w including 40%w/w On Solution In The Treatment 56 years old Caucasian male (2 type skin of the Fitzpatrick) cheek of (USP grades of Spectrum Chemical) Verruca vulgaris (wart).After the 2- propyl alcohol cleaning skin of 70%w/w, locally applied using flocking hind foot shape applicator to verrucous lesion Solubilization liquid.Pressure using strength and the application technology suitable for target lesion size apply solution about 20-30 seconds.About 1-2 points After clock, application process is repeated.This is repeated sequentially until 4 applications have been carried out.There is no pain or discomfort during process.? In next several days, the incrustation of lesion display surface and slight erythema (rubescent).Follow-up in 2 weeks shows that wart disappears completely after treatment It moves back, no erythema and without cicatrization or pigment change (hyperpigmentation or hypopigmentation) sign.8 weeks after treatment Follow-up show the recurrence of no lesion and without unfavorable beauty sequelae.Subject is very satisfied to result.

Embodiment 2

Random, double blind, blank (vehicle) control, parallel group research are carried out with 22 subjects, to assess hydrogen peroxide 40%w/w topical solution with the 2- propyl alcohol of 5%w/w is just controlling verruca vulgaris once a week (under non-first week or first) on four limbs When applying and (at most applying 4 times), with validity of the matched part compared with blank solution (solution vehicle).Treatment Scheme includes that (1) cleans target wart by the swab/wiping erasing soaked with the 2- propyl alcohol through 70%w/w；(2) with being enough to make target wart The applicator that the quantifier elimination drug wetting soaked by film provides；(3) it is applied using the pressure of strength and circular motion to target wart Add research drug about 10 seconds；(4) (or equivalent) is wiped with clean absorbability and absorb excessive research drug, with minimum pair The exposure of normal surrounding skin；(5) it is repeated application process 3 times after waiting about 20 seconds periods after applying every time. After completing to apply to the third time research drug of target wart, the non-multilated of target wart, until whole visible reactions (if there is Words) stop.After about 10 minutes, any remaining research drug is absorbed, and target wart be it is dry, without wipe It wipes or rubs.17 subjects complete the treatment of whole surroundings.Whole subjects do not report unfavorable thing to process well-tolerated Part, and local skin reaction is reported as nothing or slight.Although complete without verrucous lesion at the end of this Primary Study (4 weekly dose) Totally disappeared move back-it is anticipated that some in verrucous lesion can show improvement, but the complete healing of lesion can require over four treatments (for example, up to 10 times or up to 30 times treatment or more)-this to be that local wart is treated common (for example, daily with over the counter water The treatment of poplar acid) or will need to demonstrate lesion than more frequently applying (for example, twice a week or once a day)-once a week Statistically significantly improve and confirms Proof of Concept.Such as by improving assessment score (figure according to medical average wart 7) and by assessing measured by mean change (Fig. 8) of the score from baseline according to medical wart seriousness, subject is tight in wart Statistically significant improvement is shown in terms of principal characteristic.Following table 1, which describes wart, improves assessment score and wart seriousness assessment score.

Table 1

Embodiment 3

Carry out vitro drug release and vitro skin penetration study.Use 50%w/w FMC/PeroxyChem " Super The stabilized hydrogen peroxide stoste of D " prepares the preparation of the hydrogen peroxide of 13 kinds of 40%w/w as peroxide source, has Different 1- propyl alcohol and 2- propyl alcohol level with assess-as shown in table 2.

Table 2

Carry out vitro drug release studies with 13 kinds of preparations (based on SUPAC criterion).Receiver fluid is PBS, synthesizes film It is silicone (selected after preliminary applied research), and sample volume is 1mL, wherein supplementing 1mL.Time of measuring point For 0min, 0.5 hour, 1 hour, 2 hours, 4 hours, 6 hours and 8 hours.Fig. 1 illustrates every list after applying whole preparations The average accumulated amount of the hydrogen peroxide of plane product release.Fig. 2 and Fig. 3 has been respectively compared between propyl alcohol containing 1- and the preparation of 2- propyl alcohol Hydrogen peroxide release, it was demonstrated that the general 1- propyl alcohol increased in preparation or 2- alcohol content cause the peroxide discharged in silicone film Change the increase of the amount of hydrogen.

Although in general, after applying the preparation containing 1- propyl alcohol, discharging the peroxide of higher amount compared to 2- propyl alcohol Change hydrogen (based on w/w), but this trend it is most obvious in 1- propanol formulation and in the higher preparation of determining alcohol-from higher than about The determining alcohol of 5%w/w starts-and when determining alcohol increases to 10%w/w, 15%w/w and 20%w/w, observation reaches big Degree much.This effect is illustrated by Fig. 4 and Fig. 5, Fig. 4 show for the 1- propyl alcohol of various concentration and 2- propyl alcohol The steady state release amount of hydrogen peroxide between 0.5h and 4h, Fig. 5 are shown in 1- propyl alcohol and 2- third containing 5-20%w/w w/w level The difference of hydrogen peroxide steady state release amount between the preparation of alcohol.For the preparation containing 1- propyl alcohol, increase 1- alcohol content When hydrogen peroxide steady state release amount increase (in 0.5h to 4h), however for the preparation containing 2- propyl alcohol, hydrogen peroxide Steady state release amount seem between the concentration of the 2- propyl alcohol of test keep be basically unchanged.

Astonishing and it is essential that disclose under lower determining alcohol (for example, the alcohol for being lower than about 5%w/w), Hydrogen peroxide is greater than this effect of corresponding 2- propanol formulation from the rate of 1- propanol formulation release (0.5h-4h), wherein The rate that hydrogen peroxide is discharged from 2- propanol formulation under lower determining alcohol (for example, < 5%) is greater than hydrogen peroxide from containing 1- The rate of the preparation release of propyl alcohol.Therefore, in the preferred embodiment of most desired preparation be blended into lower determining alcohol model In enclosing, because the concentration for minimizing alcohol to be added can be minimized the potential impurity being introduced into peroxide formulations, go out Expecting ground discovery 2- propyl alcohol can be more more preferable than 1- propyl alcohol.It is not wishing to be bound by theory, it appears that under lower 2- propanol concentration The rate of release of hydrogen peroxide will be greater than the rate of release of the hydrogen peroxide under lower 1- propanol concentration.

Embodiment 4

The oxidation assessment carried out by redox potential measurement: with skin and skin is not had to t=0,1,6 and 24 hour Skin carries out oxidation assessment to the hydrogen peroxide preparation of 13 kinds of 40%w/w prepared as summarized in table 2 and (is aoxidized by measurement Reduction potential) (carrying out n=3 repetition).The oxidation of each in the 13 kinds of preparations summarized in the above table 2 is illustrated in Fig. 9 Reduction potential data.

Although for containing less than 5%w/w propyl alcohol preparation, data be not it is statistically significant, for containing There is the preparation of the propyl alcohol of 5%w/w to 20%w/w, when compared with 2- propyl alcohol, measures the higher of the preparation containing 1- propyl alcohol The redox potential of (being more positive).That is, when 1- propyl alcohol is in this concentration range (i.e. 40%) incorporation hydrogen peroxide preparation, It will have the oxidation tendency that Shi Geng great in these identical hydrogen peroxide preparations is mixed than 2- propyl alcohol.There are skin the case where Under observe similar trend, wherein the opposite redox potential between the preparation containing 1- propyl alcohol and 2- propyl alcohol is kept.Figure The 40%w/w investigated in the case where having skin and without both skin containing 5%w/w 1- propyl alcohol or 2- propyl alcohol is illustrated in 10 Hydrogen peroxide preparation redox potential research data.Therefore, although possible secondary alcohol expected in theory is (for example, 2- Propyl alcohol) it is inherently more unstable than primary alconol in the hydrogen peroxide of high concentration, but in fact, this unpredictable consequence is demonstrate,proved 2- propyl alcohol ratio 1- propyl alcohol in these embodiments is illustrated to be less likely to be oxidized, and will preferably be mixed into these solution 2- propyl alcohol.

Embodiment 5

(duplicate) had using Kruss tensometer and Wilhelmy plate technique to 13 kinds from table 2 at 37 DEG C The hydrogen peroxide preparation of the 40%w/w of different 1- propyl alcohol or 2- propanol concentration carries out surface tension analysis.Use deionized water school Barebone is shown in the result (about 70mN/m) in the literature value of 37 DEG C of 1.0mN/m.Every part of sample has 30 minutes runing times, And the mean value calculation result read by last 10.

Sample analysis is carried out in duplicate in the confidence level of 37 ± 0.5 DEG C of use ± 1.4%w/w.In the weight of acquisition Multiple junction fruit carries out third time test except this range, and calculates report using 2 immediate independent results As a result.Total data has been presented in following table 3 and has illustrated in Fig. 6.

Table 3

Data demonstrate, it is however generally that, it mixes 1- propyl alcohol or 2- propyl alcohol reduces the surface of tested hydrogen peroxide preparation Tension, and this surface tension reduces effect and the concentration of the 1- propyl alcohol of addition or 2- propyl alcohol is substantially directly proportional.Theoretically, from From the viewpoint of surface tension, may think that all to be useful in any incorporation embodiment disclosed herein.

However, 1- propyl alcohol is to the effect ratio 2- propyl alcohol of the surface tension reduction of peroxide formulations to peroxide formulations The effect that surface tension reduces is stronger, so that the preparation in preferred embodiments containing 1- propyl alcohol will have than corresponding 2- third The much lower surface tension of alcohol formulations, and will be more likely to spread out applying zone and spread from lesion, spread to week Enclose on non-lesion skin, thus weaken the validity of therapeutic agent and be used as skin in ADH substrate-cause stimulate surrounding skin Increased stimulation, erythema and unfavorable skin effects.Illustrate the peroxidating that 40%w/w is used in Journal of Sex Research and embodiment herein Hydrogen, but other hydrogen peroxide compositions by changing embodiments described here are (for example, 25%w/w, 32.5%w/ W, the concentration of hydrogen peroxide of 40%w/w, 42.5%w/w) in alcohol (for example, 2- propyl alcohol) component concentration, can readily determine that By the risk for generating the reduction of best surface tension, realizing desired clinical effectiveness and minimizing the unfavorable skin effects in part Best determining alcohol.

Embodiment 6

Use stabilized hydrogen peroxide (Peroxal CGArkema, Inc.) and 2- propyl alcohol 99%w/w (Spectrum Chemical, USP grade) prepares solution, to manufacture the stabilized hydrogen peroxide and 5%w/w that include 40%w/w 2- propyl alcohol composition and stabilized hydrogen peroxide and 5%w/w including 25%w/w 2- propyl alcohol composition.Make Solution is in the amber Pyrex screw cap vial of I type in the relative humidity for stablizing and being maintained at 25 DEG C/60%w/w (RH)；40 DEG C/75%w/w RH；Under 5 DEG C (refrigerations).The stabilized H of 25%w/w₂O₂The IPA solution of/5%w/w is at 40 DEG C Under the conditions of at 6 months and under the conditions of 25 DEG C of conditions and 5 DEG C at 24 months when keep stablize (according to the date be 2003 years 2 The existing step 4 version on the moon 6, " ICH Harmonised Tripartite Guideline:Stability Testing Of New Drug Substances and Products Q1A (R2) ", " up to specification ").40%w/w's is stabilized H₂O₂The IPA solution of/5%w/w under the conditions of 40 DEG C at 6 months when, under the conditions of 25 DEG C of conditions and 5 DEG C at 24 months when keep Stablize (the existing step 4 version for being on 2 6th, 2003 according to the date, " ICH Harmonised Tripartite Guideline:Stability Testing of New Drug Substances and Products Q1A (R2) ", " symbol Close specification ").

Embodiment 7

Use stabilized hydrogen peroxide (Peroxal CGArkema, Inc.) and 2- propyl alcohol 99%w/w (Spectrum Chemical, USP grade) prepares solution, to manufacture the stabilized hydrogen peroxide and 15%w/ that include 40%w/w The composition of the 2- propyl alcohol of the composition of the 2- propyl alcohol of w and stabilized hydrogen peroxide and 15%w/w including 25%w/w. Make solution in the amber Pyrex screw cap vial of I type in the relative humidity for stablizing and being maintained at 25 DEG C/60%w/w (RH)；40 DEG C/75%w/w RH；Under 5 DEG C (refrigerations).The stabilized H of 25%w/w₂O₂The IPA solution of/15%w/w is 40 Under the conditions of DEG C at 6 months and under the conditions of 5 DEG C of conditions and 25 DEG C at 24 months when keep stablize (according to the date be 2003 The existing step 4 version in 6 days 2 months year, " ICH Harmonised Tripartite Guideline:Stability Testing of New Drug Substances and Products Q1A (R2) ", " up to specification ").40%w/w's is steady Surely the H changed₂O₂The IPA solution of/15%w/w under the conditions of 40 DEG C at 6 months when and under the conditions of 5 DEG C of conditions and 25 DEG C 24 It keeps stablizing (the existing step 4 version for being on 2 6th, 2003 according to the date, " ICH Harmonised at a month Tripartite Guideline:Stability Testing of New Drug Substances and Products Q1A (R2) ", " up to specification ").

Embodiment 8

Using stabilized hydrogen peroxide (FMC/PeroxyChem " Super D 50% " (FMC/PeroxyChem)) and 2- propyl alcohol 99%w/w (Spectrum Chemical, USP grade) prepares solution, to manufacture the stabilized mistake for including 45%w/w The composition of the 2- propyl alcohol of hydrogen oxide and 5%w/w.It is in solution in the amber Pyrex bottle of 1 type in stablizing case Stablize and be maintained at the relative humidity (RH) of 25 DEG C/60%w/w；40 DEG C/75%w/w RH；Under 5 DEG C (refrigerations).45%w/ The stabilized H of w₂O₂The IPA solution of/5%w/w under the conditions of 40 DEG C at 6 months when and under the conditions of 5 DEG C of conditions and 25 DEG C It kept stablizing (the existing step 4 version for being on 2 6th, 2003 according to the date, " ICH Harmonised at 12 months Tripartite Guideline:Stability Testing of New Drug Substances and Products Q1A (R2) ", " up to specification ").

Embodiment 9

Using stabilized hydrogen peroxide (FMC/PeroxyChem " Super D 50% " (FMC/PeroxyChem)) and 2- propyl alcohol 99%w/w (Spectrum Chemical, USP grade) prepares solution, to manufacture the stabilized mistake for including 40%w/w The composition of the 2- propyl alcohol of hydrogen oxide and 5%w/w.Solution is distributed in the crushable glass ampule of heat-sealing.Make solution/ampoule In the chamber in the relative humidity (RH) for stablizing and being maintained at 25 DEG C/60%w/w；40 DEG C/75%w/w RH；It is (cold with 5 DEG C Hiding) under.The stabilized H of 40%w/w₂O₂The IPA solution of/5%w/w under the conditions of 5 DEG C of conditions and 25 DEG C at 12 months when so far It keeps stablizing (the existing step 4 version for being on 2 6th, 2003 according to the date, " ICH Harmonised Tripartite Guideline:Stability Testing of New Drug Substances and Products Q1A (R2) ", " symbol Close specification ").

Embodiment 10

Using stabilized hydrogen peroxide (FMC/PeroxyChem " Super D 50% " (FMC/PeroxyChem, Inc.)) and 2- propyl alcohol 99%w/w (Spectrum Chemical, USP grade) prepares solution, steady including 40%w/w to manufacture Surely the composition of the 2- propyl alcohol of the hydrogen peroxide and 5%w/w changed.It prepares solution and is distributed to amber I type Pyrex spiral shell In spiral cover bottle.Make solution be in the chamber stablize and be maintained at 25 DEG C/60%w/w relative humidity (RH) and 5 DEG C it is (cold Hiding) under the conditions of.The stabilized H of 40%w/w₂O₂The IPA solution of/5%w/w under the conditions of 25 DEG C of conditions and 5 DEG C at 12 months when It keeps stablizing (the existing step 4 version for being on 2 6th, 2003 according to the date, " ICH Harmonised Tripartite so far Guideline:Stability Testing of New Drug Substances and Products Q1A (R2) ", " symbol Close specification ").

Embodiment 11

Use stabilized hydrogen peroxide (Peroxal CGArkema, Inc.), 2- propyl alcohol 99%w/w (Spectrum Chemical, USP grade) prepares lower series preparation, and the lower series preparation includes about 44%w/w to about 46%w/w (w/ W) the 2- propyl alcohol (as shown in table 4) of stabilized hydrogen peroxide, 0%w/w or 5%w/w and including carbopol ETD 2020, the gelling agent of carbopol 974P or carbopol Ultrez 10, concentration are as shown in table 4.EDETATE SODIUM is also used as chelating agent It mixes in whole preparations, and pH is adjusted between about pH 3.5- about pH 4.0.In order to maximize peroxidating in gel preparation The level of hydrogen carries out pH adjustment step (using the triethylamine of 1%w/w and 10%w/w) after preparing preparation, and therefore table Composition (weight %w/w) in 4 is shown functionally in the actual concentrations of stable preparation.

Make preparation in chamber in the relative humidity (RH) for stablizing and being maintained at 25 DEG C/60%w/w；40 DEG C/75% w/w RH；Under 5 DEG C (refrigerations).Assess the stability of the above stabilized Peroxyl Gel preparation and based on to peroxidating The assessment of hydrogen retrieval, pH and brookfield viscosity (Brookfield viscosity) showed after t=6 weeks, carbopol ETD, blocked Pop 974P and carbopol Ultrez 10 2020 keeps its concentration of hydrogen peroxide and its chemical stability and physical stability.This The stability of kind of duration (or has additional tax for the gel preparation of two parts mixing before applying when applying or immediately The preparation of three parts of shape agent (such as 2- propyl alcohol) or more part) for be enough stability, wherein such as peroxidating Hydrogen and gelling agent are stored in individual compartment (for example, being separated by fragile article, in individual bottle, individual syringe) simultaneously And merges or mix when needed.

Embodiment 12

Applicator will have has borosilicate glass ampoule to be arranged in it by what HDPE, LDPE or HDPE/LDPE admixture were formed In applicator main body.The preparation of the 2- propyl alcohol of the hydrogen peroxide and 5%w/w of the 40%w/w of single therapeutic dose will be arranged at In ampoule.Operator will hold writing appliance in a manner of writing applicator be held in its hand to be similar to.Operator will be food Specific bit is located in cloth on the first pressure region on the outer surface for being arranged in applicator main body and opposite thumb It is placed on the second pressure region of the basic opposite side of applicator main body.Operator will be in first pressure region and second pressure area Applicator main body is squeezed with enough power using its index finger and opposite thumb between domain, so that it is intracorporal to be arranged in applicator master Ampoule fractures.Operator will move down into position of its hand in applicator the grasping section on the proximal part of applicator main body Domain.Operator makes preparation from the applicator with applicator fluid communication for squeezing in grip area by using its finger Nylon flocking hind foot shape tip release.

It will be arranged by what LDPE was formed coated with the filter for being configured to assign the hydrophobic silicone material of filter In in applicator, to filter the fragment of the ampoule from rupture.Except non-operator applies pressure to applicator main body, otherwise filter Device will prevent preparation from flowing through the filter.Operator controls the pressure of grip area is applied to by change from applicator Flow to the rate that target applies site (for example, cutaneous lesions).Then operator will treat the target lesion or many places lesion.

Embodiment 13

Use the hydrogen peroxide of (i) 45%w/w and the 2- propyl alcohol of 5%w/w, the hydrogen peroxide and 5%w/ of (ii) 40%w/w The 2- propyl alcohol of w, and (iii) with verruca vulgaris subject in blank solution (solution vehicle) preparation come into Capable random, double blind, blank (vehicle) control, parallel group research.The main purpose of this research is the two different peroxides of assessment Change hydrogen/5%w/w 2- propanol solution (H of 45%w/w₂O₂With the H of 40%w/w₂O₂) applied to the verruca vulgaris of trunk and four limbs Clinical effectiveness of the added-time compared with matched blank (vehicle).Secondary objective is assessment hydrogenperoxide steam generator to verruca vulgaris Safety when application compared with blank (vehicle).If subject has at least one target wart, institute on trunk or four limbs It states target wart and assesses (PWA) >=2 with (i) its longest axis >=3mm and≤10mm, (ii) thickness≤3mm, and (iii) doctor's wart, Then subject is included into research.It is recruited with the subject for just controlling both wart and duration/recurrent wart into clinical test.

90 subjects complete to study and be randomized into the following group: 1st group: 45%w/w solution (n=32)；2nd Group: 40% w/w solution (n=31)；3rd group: blank solution (solution vehicle) (n=27).It treats once a week Subject amounts to 8 treatments.Then subject taken back treating latter week for the last time, is commented with carrying out effect and safety Estimate (the 10th time medical).Then subject continues the non-blind of the research of additional 11 weeks (12 weeks after finally treatment is medical) Partially (, to assess the duration of clinical effectiveness.

The Primary Endpoint of research be using the analysis of covariance when the 10th time medical mean change of the PWA score from baseline. PWA is determined, as shown in table 5:

The ratio between least squares means progress blank (vehicle) and each treatment group is used based on each scheme group Compared with.Secondary endpoints include two respondent's analyses: being judged as the ratio of the patient removed according to PWA target wart when the 10th time medical Example；And removing or the almost ratio of unconspicuous patient are judged as according to PWA target wart when the 10th time medical.Use card side Statistic (Chi Square statistic) carries out two kinds of respondent's analyses to each scheme group.Carry out other exploration Analysis, to observe the ratio of the reduced subject for 2 ordinal numbers for realizing PWA score when the 10th time medical.

As shown in Figure 12 and Figure 14, compared to placebo, shown with the patient that the hydrogenperoxide steam generator of 45%w/w is treated The statistically significant variation (p=0.01) of PWA score.In addition, as shown in Figure 13 and Figure 15, compared to placebo, The H of 45%w/w₂O₂Topical solution in terms of fully erased (Figure 13) of wart and is realized and is removed or slight when the 10th time medical PWA score (Figure 15) in terms of reach statistical conspicuousness (p=0.02).Figure 16 show statistically significant ratio by Examination person is also in the H with 45%w/w₂O₂Topical solution realizes the reduction of 2 ordinal numbers of PWA score when the 10th time medical.40% The H of w/w₂O₂The H of topical solution (Figure 19) and 45%w/w₂O₂Local skin reaction and the sky of both topical solutions (Figure 18) White (vehicle) is similar (Figure 20).As shown in Figure 17, the instantaneous local skin slightly to moderate is only observed during treatment Reaction.Treatment tolerance is very good, and the adverse events of most frequent report are slight erythema in treatment group.Therefore, 45%w/w H₂O₂Topical solution is proved to be safe and efficient treatment statistically significant for verruca vulgaris.It is astonishing and exceed Expect, the H compared to 40%w/w₂O₂Topical solution, the H of 45%w/w₂O₂Topical solution shows product significant in this way Pole result.Although the H of 40%w/w₂O₂Topical solution is when compared with blank (vehicle) without aobvious in terms of wart seriousness Show statistically significant improvement, but the H of 45%w/w₂O₂Topical solution is not only shown when compared with blank (vehicle) Statistically significant improvement, and can be removed during treatment about 25%w/w wart and be resistant to it is very good.

The final follow-up (the 13rd time medical) of the non-blind part of research is extended than major efficacy endpoint (the 10th time medical) Additional 11 weeks, so as to after final treatment phase 12 weeks assessment treatment groups compared to the clinical effectiveness that blank (vehicle) is organized Duration.The persistence (maintenance of " removing "-PWA=0) of response when final medical is maintained at the 10th time just It is the H of the 45%w/w of respondent when examining₂O₂The subject of 87.5%w/w in treatment group.It is respondent when the 10th time medical The H of 40%w/w₂O₂Single subject in treatment group is still respondent when the 13rd time medical.These subjects finally with The maintenance of clinical removing/healing to target verrucous lesion is demonstrated when visit.

Embodiment 14

Using stabilized hydrogen peroxide (FMC/PeroxyChem " Super D 50% " (FMC/PeroxyChem, Inc.)) and 2- propyl alcohol 99%w/w (Spectrum Chemical, USP grade) prepares solution, steady including 45%w/w to manufacture Surely the composition of the 2- propyl alcohol of the hydrogen peroxide and 5%w/w changed.It prepares solution and equal part (2.2ml) arrives 9mm diameter ampoule In.Solution is in the chamber to stablize and be maintained at the relative humidity (RH) of 40 DEG C/75%w/w, 25 DEG C/60%w/w Under the conditions of RH and 5 DEG C (refrigeration).The stabilized H of 45%w/w₂O₂The IPA solution of/5%w/w is under the conditions of all three: Under the conditions of 40 DEG C at 6 months (Figure 23) and under 25 DEG C of conditions (Figure 22) and 5 DEG C of conditions (Figure 21) at 12 months when so far It keeps stablizing (the existing step 4 version for being on 2 6th, 2003 according to the date, " ICH Harmonised Tripartite Guideline:Stability Testing of New Drug Substances and Products Q1A (R2) ", " symbol Close specification ").

Embodiment 15

Use the hydrogen peroxide of (i) 45%w/w and the 2- propyl alcohol of 5%w/w, and (ii) with 8 years old of verruca vulgaris and with On pediatric subject and both Adult human subjects in blank solution (solution vehicle) preparation come carry out it is random, Double blind, blank (vehicle) control, parallel group research.Adult human subjects self will apply research drug, and pediatric subject Research drug will be applied by parent or guardian.The main purpose of this research is to assess hydrogen peroxide/5%w/w of 45%w/w 2- propanol solution applies from subject oneself to the verruca vulgaris of trunk and four limbs up to eight weeks (once a week or twice a week) When validity compared with matched blank (vehicle).Secondary objective is to assess hydrogen peroxide/5%w/w of 45%w/w Clinical effectiveness of the 2- propanol solution when applying twice a week up to eight weeks to all treated wart (target adds non-target) is to comment Estimate the duration of response of wart (target wart adds non-target wart) all treated up to three months after final research drug applies, And be assess 45%w/w hydrogen peroxide/5%w/w 2- propanol solution when applying to verruca vulgaris with blank (vehicle) The safety compared.The subject being included into research will have target wart, the target from one to six on trunk and four limbs Wart has (i) its longest axis >=3mm and≤8mm, (ii) thickness≤3mm, and (iii) doctor's wart assessment (PWA) >=2.It suffers from Just controlling the pediatric subject (age > 8 years old) of both wart and duration/recurrent wart and Adult human subjects will be recruited into clinic Test.

Subject will be treated once a week or twice a week, amounted to up to 8 weeks (8 or 16 drugs apply).It was studying Cheng Zhong, subject will be brought back to carry out regular follow-up and assessment, and will treat for the last time be brought back in latter week with into Row efficacy and saferry assessment (the 10th time medical).Then subject will continue (finally to treat and go to a doctor it for additional 11 weeks 12 weeks afterwards) research, to assess the duration of the clinical effectiveness maintenance of " removing "-PWA=0 (include).

The Primary Endpoint of research will be using the analysis of covariance when the 10th time medical PWA score (table 5) from baseline Mean change.

Blank will be carried out compared between treatment group using least squares means based on each scheme group.Secondary endpoints Two respondent's analyses will be included: when the 10th time medical, target wart is judged as the ratio of the patient of removing according to PWA；And 10th time it is medical when target wart be judged as removing according to PWA or the almost ratio of unconspicuous patient.Chi-square statistics amount will be used Two kinds of respondent's analyses are carried out to each scheme group.Other exploratory analysis will be carried out, to observe when the 10th time medical Realize the ratio of the reduced subject of 2 ordinal numbers of PWA score.

Compared to placebo, once a week and weekly two with the 2- propanol solution of the hydrogen peroxide of 45%w/w and 5%w/w Both pediatric patients and adult patient of secondary treatment are expected the statistically significant variation of display PWA score.In addition, comparing In placebo, the hydrogen peroxide of 45%w/w and the 2- propyl alcohol topical solution of 5%w/w are expected at final research drug and apply The latter week of (the 10th time medical) in terms of fully erased (PWA=0) of wart and realize remove or slight PWA score in terms of reach To statistical conspicuousness.Additionally, it is contemplated that the subject of statistically significant ratio will also be in the H with 45%w/w₂O₂Part The reduction of 2 ordinal numbers of PWA score is realized when the 10th time medical with solution.With the hydrogen peroxide of 45%w/w and 5%w/w 2- propanol solution local skin reaction be expected it is similar with blank, wherein it is contemplated that treatment during only observe slightly to moderate Instantaneous local skin reaction.

Treatment is expected to well-tolerated.Therefore, it is contemplated that the hydrogen peroxide of 45%w/w and the 2- propanol solution of 5%w/w It will be proved to apply up to eight once a week or twice a week by subject oneself (or parent or guardian of minor) It is statistically significant peace for the pediatric subject for suffering from single verruca vulgaris or a variety of verruca vulgarises and/or Adult human subjects when all Complete and effective treatment, and will to be lasting-i.e.-maintain (finally studies drug when finally studying Follow-up visits for this response 12 weeks after application).

It is still further contemplated that since the hydrogen peroxide of 45%w/w and the 2- propanol solution of 5%w/w are as its mechanism of action A part can induce local immune response and/or general immunity response (that is, verruca vulgaris), not the hydrogen peroxide of 45%w/w Some improvement and/or completely recession can also be shown by being applied directly to the verruca vulgaris with the 2- propanol solution of 5%w/w.It is also pre- Phase shows that in this case response (fully erased or improvement) is also lasting (as described above).

Although having referred to certain preferred embodiments of the invention has been described in detail the present invention, other versions It is possible.Therefore, the spirit and scope of the appended claims be not limited to the description contained in this specification and preferably Version.

Claims (30)

1. a kind of method for treating wart or wart related conditions in subject in need, the method includes to the subject Application includes the topical compositions of the hydrogen peroxide greater than 40%w/w to about 70%w/w.

2. the method as described in claim 1, wherein the topical compositions include about 45%w/w, about 50%w/w, about The hydrogen peroxide of the amount of the range of 54%w/w, about 55%w/w, about 59%w/w or any two in these values.

3. the method as described in claim 1, wherein the topical compositions further include being greater than 0%w/w to about 15%w/w 2- propyl alcohol.

4. the method as described in claim 1, wherein the topical compositions further include being greater than 0%w/w to about 5%w/w 2- propyl alcohol.

5. the method as described in claim 1, wherein the wart or wart related conditions are selected from by verruca vulgaris, verruca filiformis, genitals Wart, external genital organs wart, condyloma acuminatum, recurrent wart, duration wart, periungual wart, subungual wart, plantar wart, mosaic warts, intractable wart, Just control wart, palmoplantar verruca, verruca plana, epidermodysplasia verruciformis correlation wart, butcher's wart, oropharynx wart, larynx wart, papilloma of larynx, larynx Dysplasia, anogenital wart, cervical atypical hyperplasia, uterine neck wart, uterine neck tumor-like lesion, or combinations thereof group.

6. the method as described in claim 1, wherein the operation of applying said compositions is combined with other methods, its described other party Method mechanically, physically or chemically enhances infiltration of the hydrogen peroxide into lesion or can enhance described group in another way Close the therapeutic efficiency of object.

7. method as claimed in claim 6, wherein mechanically enhancing the operation packet of infiltration of the hydrogen peroxide into the lesion It includes and polishes the treatment site of the subject, frustrates, striking off or debridement.

8. method as claimed in claim 6, wherein mechanically enhancing hydrogen peroxide penetrates into treatment site into lesion Operation can application before the application of the composition, after the application of the composition or with the composition simultaneously Occur.

9. the method as described in claim 1, wherein the operation of applying said compositions is once a day, twice daily, weekly Once, twice a week, every other week it is primary, every other day primary, monthly, the every two moon is primary, every three months is primary or By packaging or doctor's guidance, to realize desired clinical effectiveness.

10. the method as described in claim 1, wherein applying said compositions at least about one week, at least about two weeks, at least about three Week, at least about surrounding, at least about five weeks, at least about six weeks, at least about seven weeks, at least about eight weeks, at least about nine weeks, at least about ten Week, at least about 11 weeks, at least about 12 weeks, at least about one month, at least about two months, at least about three months, at least about four A month, at least about five months, at least about six months, the range of any two in these values or until lesion subsides.

11. the method as described in claim 1, wherein hydrogen peroxide is active pharmaceutical ingredient grade (API) grade hydrogen peroxide.

12. the method as described in claim 1, the method also includes applying second chamber to the subject, described the Two compositions include 2- propyl alcohol of the about 25%w/w to the hydrogen peroxide of about 70%w/w and greater than 0%w/w to about 15%w/w.

13. the method as described in claim 1, the method also includes applying second chamber to the subject, described the Two compositions include 2- propyl alcohol of the about 25%w/w to the hydrogen peroxide of about 70%w/w and greater than 0%w/w to about 5%w/w.

14. method as claimed in claim 13, wherein at least about 1 day after the initial application of the topical compositions, At least about 2 days, at least about 3 days, at least about 1 week, at least about 2 weeks, at least about 3 weeks, at least about 4 weeks, at least one moon, at least two A month, at least three months, at least four moon, at least five moon or at least six moon apply the second chamber.

15. the method as described in claim 1, wherein the topical compositions are solution or gel.

16. the method as described in claim 1, wherein the operation of applying said compositions includes connecing treatment site with applicator Touching, the applicator be selected from by sponge, swab, foam head stick, cotton balls, brush, Woven fabric or supatex fabric, roll of gauze, Gauze, gloves, pen type applicator, flocking hind foot applicator, or combinations thereof group.

17. the method as described in claim 1, wherein the operation of applying said compositions includes making treatment site and applicator Nib contacts, wherein the applicator includes: frangible ampoule, applicator main body, applicator hub, tip and filter, it is described Frangible ampoule has the composition being set in the frangible ampoule, and the applicator main body, which has, is arranged in the application The frangible ampoule in device main body, the applicator hub are connected to the applicator body fluid, and the tip is arranged in institute The proximal end of applicator hub is stated, the filter is arranged between the frangible ampoule and the tip.

18. method as claimed in claim 17, wherein the applicator have mechanically or physically enhancing hydrogen peroxide to Infiltration in lesion or enhance in another way the composition therapeutic efficiency feature.

19. method as claimed in claim 18, wherein the feature of the applicator is directed at the topical compositions Application before polish the treatment site of the subject, file, striking off or debridement.

20. a kind of method for treating verruca vulgaris in subject in need, the method includes locally applying to the subject With include greater than 40%w/w to about 70%w/w hydrogen peroxide topical compositions.

21. method as claimed in claim 20, wherein the topical compositions include about 45%w/w, about 50%w/w, about The hydrogen peroxide of the amount of the range of 54%w/w, about 55%w/w, about 59%w/w or any two in these values.

22. method as claimed in claim 20, wherein the topical preparation further includes being greater than 0%w/w to about 15%w/w 2- propyl alcohol.

23. method as claimed in claim 20, wherein the topical preparation further includes being greater than 0%w/w to about 5%w/w 2- propyl alcohol.

24. method as claimed in claim 20, wherein the topical compositions include the hydrogen peroxide of the amount of about 45%w/w The 2- propyl alcohol of the amount of about 5%w/w.

25. method as claimed in claim 20, wherein the operation for applying the topical compositions is once a week or weekly Twice.

26. method as claimed in claim 20, the method also includes applying additional therapeutic modality, the additional treatment Mode includes the second hydrogen peroxide preparation, adjuvant, inhibitor, adhesive tape removing, cold therapy, electrosurgery, curettage, laser treatment Method, salicylic acid, trichloroacetic acid, podophyllin, cantharidin, 5 FU 5 fluorouracil, bleomycin, part imiquimod, in lesion Candida antigens, part use side dibutyl phthalate, the laser for taking orally Cimetidine, the removal of surgery lesion, electrodesiccation, various wavelength (ablative and non-ablative), RF ablation, curettage, operation excision, ablation agent, chemical strippers, upset lesion at dermabrasion Surface, the thickness for reducing lesion or size or total volume, the surface area for increasing lesion, or combinations thereof.

27. a kind of for treating the kit of wart, the kit includes container, and the container includes being greater than 40%w/w to about The hydrogen peroxide and amount of 70%w/w is the 2- propyl alcohol greater than 0% to about 5%.

28. kit as claimed in claim 27, the kit further includes applicator.

29. kit as claimed in claim 28, wherein the applicator, which has, mechanically enhances hydrogen peroxide into lesion Infiltration or can be enhanced in another way the composition therapeutic efficiency feature.

30. kit as claimed in claim 27, the kit further include be intended to the treatment site of subject into Row polishes, files, striking off or the material or applicator of the feature of debridement.